Is DNAH3 p.Ala876Val (c.2627C>T) pathogenic?

DNAH3 p.Ala876Val (c.2627C>T) is classified Uncertain significance in DNAH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely benign (0.1485); Very rare (popmax 8.48e-05%, nfe).

How common is DNAH3 p.Ala876Val (c.2627C>T) in the general population?

DNAH3 p.Ala876Val (c.2627C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DNAH3 p.Ala876Val (c.2627C>T)?

AlphaMissense predicts likely benign (score 0.1485) — an in-silico prediction, not a clinical call.

DNAH3 p.Ala876Val

c.2627C>T · VCV3503459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1485 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1485	likely benign
REVEL	0.077	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 8.2	GERP 2, phastCons 1
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A922V vs ClinVar A876V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,940 alleles

Overall 6.84e-05% 1/1,461,770 alleles · very rare

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: DNAH3
Protein: p.Ala876Val
Coding: c.2627C>T
MANE Select: NM_001347886
Type: single nucleotide variant
Location: chr16:21086961 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 876: the 'stem' region

Full DNAH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH3 p.Ala876Ser Uncertain significance ★ ⚠ same residue
DNAH3 p.Ala1918Gly Uncertain significance ★★ ⚠ same type
DNAH3 p.Arg1228Gln Uncertain significance ★★ same type
DNAH3 p.Arg635Gln Uncertain significance ★★ same type
DNAH3 p.Asn1728Ser Uncertain significance ★★ ⚠ same type
DNAH3 p.Asp3656Asn Uncertain significance ★★ same type
DNAH3 p.Leu2597Val Uncertain significance ★★ same type
DNAH3 p.Leu4044Phe Uncertain significance ★★ ⚠ same type

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/dnah3-p-ala876val (accessed [today's date]).

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