Is DNAH7 p.Asp1248Val (c.3743A>T) pathogenic?

DNAH7 p.Asp1248Val (c.3743A>T) is classified Uncertain significance in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely pathogenic (0.9552); Very rare (popmax 0.00267%, afr).

How common is DNAH7 p.Asp1248Val (c.3743A>T) in the general population?

DNAH7 p.Asp1248Val (c.3743A>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DNAH7 p.Asp1248Val (c.3743A>T)?

AlphaMissense predicts likely pathogenic (score 0.9552) — an in-silico prediction, not a clinical call.

DNAH7 p.Asp1248Val

c.3743A>T · rs1447314713 · VCV2487151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9552 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.9552	likely pathogenic
REVEL	0.63	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	25.0	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 0.00267% African / African-American · 2/74,900 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,972 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,450
European (non-Finnish)	8.47e-05%	1,179,998

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: DNAH7
Protein: p.Asp1248Val
Coding: c.3743A>T
MANE Select: NM_018897
dbSNP: rs1447314713
Type: single nucleotide variant
Location: chr2:195923677 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Residue 1248: the 'stem' region

Full DNAH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH7 p.Arg1884Gln Uncertain significance ★★ ⚠ same type
DNAH7 p.Arg3272Gln Uncertain significance ★★ ⚠ same type
DNAH7 p.Asn2116Ser Uncertain significance ★★ ⚠ same type
DNAH7 p.Asp1219Gly Uncertain significance ★★ ⚠ same type
DNAH7 p.Asp1787Gly Uncertain significance ★★ same type
DNAH7 p.Asp2867Tyr Uncertain significance ★★ ⚠ same type
DNAH7 p.Ile1203Met Uncertain significance ★★ ⚠ same type
DNAH7 p.Leu1715Met 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/dnah7-p-asp1248val (accessed [today's date]).

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