Is DNAH12 p.Pro77Ser (c.229C>T) pathogenic?

DNAH12 p.Pro77Ser (c.229C>T) is classified Uncertain significance in DNAH12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.0943); Very rare (popmax 0.00113%, sas).

How common is DNAH12 p.Pro77Ser (c.229C>T) in the general population?

DNAH12 p.Pro77Ser (c.229C>T) is very rare (popmax 0.00113%, sas) (gnomAD).

What do computational predictors say about DNAH12 p.Pro77Ser (c.229C>T)?

AlphaMissense predicts likely benign (score 0.0943) — an in-silico prediction, not a clinical call.

DNAH12 p.Pro77Ser

c.229C>T · rs2530732522 · VCV3083541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0943	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 90 kb · p 0.023 · regional, not allelic
Overall
CADD	15.67	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,696 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00081% 13/1,605,194 alleles · very rare exomes 13/1,453,002 · genomes 0/152,192 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00113%	88,696
European (non-Finnish)	0.00102%	98,081

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: DNAH12
Protein: p.Pro77Ser
Coding: c.229C>T
MANE Select: NM_001366028
dbSNP: rs2530732522
Type: single nucleotide variant
Location: chr3:57523826 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Residue 77: the 'stem' region

Full DNAH12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH12 c.1650+6G>A Benign ★★ same type
DNAH12 c.1912-8A>G Benign ★★ same type
DNAH12 c.3053+9A>G Benign ★★ same type
DNAH12 c.5253+263A>T Benign ★★ same type
DNAH12 c.5253+289C>T Benign ★★ same type
DNAH12 c.6948+922= Benign ★★ same type
DNAH12 p.Asp1572Asn Benign ★★ same type
DNAH12 p.Asp224Glu Benign ★★ 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/dnah12-p-pro77ser (accessed [today's date]).

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