Is DNAH8 p.Ser2970Phe (c.8909C>T) pathogenic?

DNAH8 p.Ser2970Phe (c.8909C>T) is classified Conflicting classifications of pathogenicity in DNAH8 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1404); Rare (popmax 0.54%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Ser2970Phe (c.8909C>T)?

DNAH8 p.Ser2970Phe (c.8909C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Ser2970Phe (c.8909C>T) in the general population?

DNAH8 p.Ser2970Phe (c.8909C>T) is rare (popmax 0.54%, 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 DNAH8 p.Ser2970Phe (c.8909C>T)?

AlphaMissense predicts likely benign (score 0.1404) — an in-silico prediction, not a clinical call.

DNAH8 p.Ser2970Phe

c.8909C>T · rs150571615 · VCV414375

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1404 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.54%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1404	likely benign
REVEL	0.072	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP 0.5, phastCons 0.001
Regional constraint	o/e 0.92	unconstrained · MANE · 41 kb · p 0.0093 · regional, not allelic
Overall
CADD	14.97	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S2753F vs ClinVar S2970F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.54% African / African-American · 405/75,016 alleles

Filtering AF 0.496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.479%

Overall 0.0297% 480/1,613,978 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.54%	185
Remaining individualsnot grpmax-eligible	0.0544%	1,838
Admixed American	0.0467%	2,143
South Asian	0.0022%	45,517
European (non-Finnish)	0.000932%	107,268

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: DNAH8
Protein: p.Ser2970Phe
Coding: c.8909C>T
MANE Select: NM_001206927
dbSNP: rs150571615
Type: single nucleotide variant
Location: chr6:38896194 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Residue 2970: a UniProt-annotated variant site (found in a patient with primary ciliary dyskinesia; uncertain significance); the 'aaa 4' region

Full DNAH8 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

DNAH8 c.10963-1G>A Likely pathogenic ★★ same condition
DNAH8 c.11563+1G>T Likely pathogenic ★★ same condition
DNAH8 c.2664+2T>C Likely pathogenic ★★ same condition
DNAH8 c.5734-1G>T Likely pathogenic ★★ same condition
DNAH8 p.Arg1090Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg2878Ter Pathogenic ★★ same condition
DNAH8 p.Arg4166Ter 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/dnah8-p-ser2970phe (accessed [today's date]).

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