Is DNAH7 p.Ser438Asn (c.1313G>A) pathogenic?

DNAH7 p.Ser438Asn (c.1313G>A) is classified Benign in DNAH7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1389); Common (popmax 8.23%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DNAH7 p.Ser438Asn (c.1313G>A)?

AlphaMissense predicts likely benign (score 0.1389) — an in-silico prediction, not a clinical call.

DNAH7 p.Ser438Asn

Q: How common is DNAH7 p.Ser438Asn (c.1313G>A) in the general population?

DNAH7 p.Ser438Asn (c.1313G>A) is common (popmax 8.23%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1313G>A · rs16843720 · VCV791883

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1389 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.23%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1389	likely benign
REVEL	0.039	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 3.3	GERP 1.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	18.32	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 8.23% African / African-American · 6,090/74,042 alleles

Filtering AF 8.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.98%

Overall 0.422% 6,704/1,590,374 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.23%	12
Remaining individualsnot grpmax-eligible	0.46%	217
Admixed American	0.429%	233
Middle Eastern	0.134%	745
South Asian	0.0117%	8,577
European (non-Finnish)	0.00582%	17,186

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.Ser438Asn
Coding: c.1313G>A
MANE Select: NM_018897
dbSNP: rs16843720
Type: single nucleotide variant
Location: chr2:196000744 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Residue 438: the 'stem' region; a UniProt-annotated variant site (in)

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-ser438asn (accessed [today's date]).

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