Is DNAH11 p.Arg3477Ser (c.10431A>C) pathogenic?

DNAH11 p.Arg3477Ser (c.10431A>C) is classified Conflicting classifications of pathogenicity in DNAH11 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-12-28). AlphaMissense: likely benign (0.2687); Very rare (popmax 0.00267%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH11 p.Arg3477Ser (c.10431A>C)?

DNAH11 p.Arg3477Ser (c.10431A>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH11 p.Arg3477Ser (c.10431A>C) in the general population?

DNAH11 p.Arg3477Ser (c.10431A>C) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAH11 p.Arg3477Ser (c.10431A>C)?

AlphaMissense predicts likely benign (score 0.2687) — an in-silico prediction, not a clinical call.

DNAH11 p.Arg3477Ser

c.10431A>C · rs578086869 · VCV2141678

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.2687	likely benign
REVEL	0.237	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.81	GERP -5.9
Regional constraint	o/e 1.28	unconstrained · MANE · 358 kb · p 1.1e-96 · regional, not allelic
Overall
CADD	14.03	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,024 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00136% 22/1,613,400 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,238
African / African-Americangrpmax	0.00267%	37,512
Admixed American	0.00167%	59,882
European (non-Finnish)	0.00144%	69,397

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DNAH11
Protein: p.Arg3477Ser
Coding: c.10431A>C
MANE Select: NM_001277115
dbSNP: rs578086869
Type: single nucleotide variant
Location: chr7:21816565 (GRCh38)
Gene constraint: LOEUF 0.912 · pLI <0.01 (gnomAD)
Residue 3477: the 'aaa 5' region

Full DNAH11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAH11 c.10166-1G>C Likely pathogenic ★★ same condition
DNAH11 c.10569-2A>G Likely pathogenic ★★ same condition
DNAH11 c.10691+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.10896+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.11203-1G>C Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.11839+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.12934-1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.1710+1G>C Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dnah11-p-arg3477ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown