Is DNAH2 p.Ala3233Val (c.9698C>T) pathogenic?

DNAH2 p.Ala3233Val (c.9698C>T) is classified Uncertain significance in DNAH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.1041); Ultra-rare (popmax 0.0209%, sas); Associated with Inborn genetic diseases.

What condition is associated with DNAH2 p.Ala3233Val (c.9698C>T)?

DNAH2 p.Ala3233Val (c.9698C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH2 p.Ala3233Val (c.9698C>T) in the general population?

DNAH2 p.Ala3233Val (c.9698C>T) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

What do computational predictors say about DNAH2 p.Ala3233Val (c.9698C>T)?

AlphaMissense predicts likely benign (score 0.1041) — an in-silico prediction, not a clinical call.

DNAH2 p.Ala3233Val

c.9698C>T · VCV4617608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1041 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1041	likely benign
REVEL	0.292	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 4.5e-10 · 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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% South Asian · 19/91,088 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00273% 44/1,612,616 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,794
Middle Eastern	0.0165%	6,060
African / African-American	0.012%	8,338
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Finnishnot grpmax-eligible	0.0016%	62,538
European (non-Finnish)	0.00102%	98,331

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: DNAH2
Protein: p.Ala3233Val
Coding: c.9698C>T
MANE Select: NM_020877
Type: single nucleotide variant
Location: chr17:7807555 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 3233: the 'stalk' region

Full DNAH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAH2 p.Ala3233= Likely benign ★★ same residue
DNAH2 p.Ala1036Val Uncertain significance ★★ ⚠ same condition
DNAH2 p.Arg1533Cys Uncertain significance ★★ ⚠ same condition
DNAH2 p.Arg2538Gln Uncertain significance ★★ same condition
DNAH2 p.Arg3759His Uncertain significance ★★ ⚠ same condition
DNAH2 p.Gln2069Glu Uncertain significance ★★ same condition
DNAH2 p.Ile4043Ser Uncertain significance ★★ ⚠ same condition
DNAH2 p.Pro3819Leu Uncertain significance ★★ ⚠ 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/dnah2-p-ala3233val (accessed [today's date]).

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