Is DNAH3 p.Ser475Phe (c.1424C>T) pathogenic?

DNAH3 p.Ser475Phe (c.1424C>T) is classified Likely benign in DNAH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). AlphaMissense: likely benign (0.3314); Rare (popmax 0.891%, mid).

How common is DNAH3 p.Ser475Phe (c.1424C>T) in the general population?

DNAH3 p.Ser475Phe (c.1424C>T) is rare (popmax 0.891%, mid) (gnomAD).

What do computational predictors say about DNAH3 p.Ser475Phe (c.1424C>T)?

AlphaMissense predicts likely benign (score 0.3314) — an in-silico prediction, not a clinical call.

DNAH3 p.Ser475Phe

c.1424C>T · rs140516491 · VCV3024879

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3314 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.891%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.3314	likely benign
REVEL	0.196	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S504F vs ClinVar S475F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.891% Middle Eastern · 54/6,062 alleles

Filtering AF 0.701% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.657%

Overall 0.565% 9,123/1,613,820 alleles · rare exomes 8,517/1,461,556 · genomes 606/152,264 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.891%	112
European (non-Finnish)	0.674%	148
Admixed American	0.612%	163
Remaining individualsnot grpmax-eligible	0.534%	187
South Asian	0.317%	316
African / African-American	0.132%	758
Finnishnot grpmax-eligible	0.0297%	3,369
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
East Asian	0.00223%	44,872

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.Ser475Phe
Coding: c.1424C>T
MANE Select: NM_001347886
dbSNP: rs140516491
Type: single nucleotide variant
Location: chr16:21122018 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)

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-ser475phe (accessed [today's date]).

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