Is DNAH12 p.Asp1826Val (c.5477A>T) pathogenic?

DNAH12 p.Asp1826Val (c.5477A>T) is classified Uncertain significance in DNAH12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1001); Very rare (popmax 0.00274%, afr).

How common is DNAH12 p.Asp1826Val (c.5477A>T) in the general population?

DNAH12 p.Asp1826Val (c.5477A>T) is very rare (popmax 0.00274%, afr) (gnomAD).

What do computational predictors say about DNAH12 p.Asp1826Val (c.5477A>T)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

DNAH12 p.Asp1826Val

c.5477A>T · rs1001394819 · VCV3083567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00274%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.17	GERP -3.5
Regional constraint	o/e 1.01	unconstrained · MANE · 159 kb · p 0.54 · regional, not allelic
Overall
CADD	16.19	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D1807V vs ClinVar D1826V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00274% African / African-American · 2/73,048 alleles

Filtering AF 0.000454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00017%

Overall 0.000193% 3/1,551,574 alleles · very rare exomes 1/1,399,366 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00274%	36,524
European (non-Finnish)	8.72e-05%	1,146,990

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.Asp1826Val
Coding: c.5477A>T
MANE Select: NM_001366028
dbSNP: rs1001394819
Type: single nucleotide variant
Location: chr3:57421603 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)

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-asp1826val (accessed [today's date]).

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