Is DNAH8 p.Glu972Val (c.2915A>T) pathogenic?

DNAH8 p.Glu972Val (c.2915A>T) is classified Benign in DNAH8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.3082); Low-frequency (popmax 3.42%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Glu972Val (c.2915A>T)?

DNAH8 p.Glu972Val (c.2915A>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Glu972Val (c.2915A>T) in the general population?

DNAH8 p.Glu972Val (c.2915A>T) is low-frequency (popmax 3.42%, sas) (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.Glu972Val (c.2915A>T)?

AlphaMissense predicts likely benign (score 0.3082) — an in-silico prediction, not a clinical call.

DNAH8 p.Glu972Val

c.2915A>T · rs139961713 · VCV224928

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3082 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.42%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.3082	likely benign
REVEL	0.175	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 131 kb · p 0.0001 · regional, not allelic
Overall
CADD	22.4	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 E755V vs ClinVar E972V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.42% South Asian · 2,981/87,104 alleles

Filtering AF 3.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.28%

Overall 0.33% 5,283/1,599,432 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	3.42%	29
East Asian	3.01%	33
Middle Eastern	0.905%	111
Remaining individualsnot grpmax-eligible	0.426%	235
Admixed American	0.131%	762
European (non-Finnish)	0.0469%	2,134
African / African-American	0.0241%	4,141
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,333

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.Glu972Val
Coding: c.2915A>T
MANE Select: NM_001206927
dbSNP: rs139961713
Type: single nucleotide variant
Location: chr6:38803192 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Residue 972: a UniProt-annotated variant site (found in a patient with primary ciliary dyskinesia; uncertain significance)

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-glu972val (accessed [today's date]).

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