Is DNAH3 p.Ala12Thr (c.34G>A) pathogenic?

DNAH3 p.Ala12Thr (c.34G>A) is classified Benign in DNAH3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0752); Common (popmax 6.39%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DNAH3 p.Ala12Thr (c.34G>A)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

DNAH3 p.Ala12Thr

Q: How common is DNAH3 p.Ala12Thr (c.34G>A) in the general population?

DNAH3 p.Ala12Thr (c.34G>A) is common (popmax 6.39%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.34G>A · rs58508496 · VCV776992

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.39%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.049	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 -3.7	GERP -5.6
Overall
CADD	0.004	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 A41T vs ClinVar A12T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.39% African / African-American · 4,772/74,712 alleles

Filtering AF 6.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.17%

Overall 0.384% 6,174/1,609,724 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.39%	16
Middle Eastern	0.611%	164
Admixed American	0.527%	190
Remaining individualsnot grpmax-eligible	0.452%	221
European (non-Finnish)	0.0616%	1,623
South Asian	0.0308%	3,249
East Asian	0.029%	3,449
Finnishnot grpmax-eligible	0.00156%	63,970

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.Ala12Thr
Coding: c.34G>A
MANE Select: NM_001347886
dbSNP: rs58508496
Type: single nucleotide variant
Location: chr16:21146085 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 12: the 'stem' region; the 'disordered' region

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

Similar variants

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
DNAH3 p.Lys374Gln 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-ala12thr (accessed [today's date]).

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