Is DNAH10 p.Ser228Pro (c.682T>C) pathogenic?

DNAH10 p.Ser228Pro (c.682T>C) is classified Benign in DNAH10 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-04-19). AlphaMissense: likely benign (0.0638); Common (popmax 94.9%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DNAH10 p.Ser228Pro (c.682T>C)?

AlphaMissense predicts likely benign (score 0.0638) — an in-silico prediction, not a clinical call.

DNAH10 p.Ser228Pro

Q: How common is DNAH10 p.Ser228Pro (c.682T>C) in the general population?

DNAH10 p.Ser228Pro (c.682T>C) is common (popmax 94.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.682T>C · rs11057353 · VCV402611

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0638 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 94.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0638	likely benign
REVEL	0.071	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 -6	GERP -2.6
Overall
CADD	0.062	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S167P vs ClinVar S228P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 94.9% East Asian · 42,595/44,870 alleles

Filtering AF 94.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 93.9%

Overall 63.1% 1,018,650/1,613,600 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	94.9%	1
Admixed American	69.7%	1
Ashkenazi Jewishnot grpmax-eligible	68.6%	1
South Asian	67.3%	1
Finnishnot grpmax-eligible	66.7%	1
Remaining individualsnot grpmax-eligible	64.4%	2
European (non-Finnish)	61.4%	2
Middle Eastern	59.4%	2
Amishnot grpmax-eligible	59.3%	2
African / African-American	55.9%	2

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: DNAH10
Protein: p.Ser228Pro
Coding: c.682T>C
MANE Select: NM_001372106
dbSNP: rs11057353
Type: single nucleotide variant
Location: chr12:123781140 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Residue 228: the 'stem' region

Full DNAH10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH10 p.Ala2444Val Uncertain significance ★★ ⚠ same type
DNAH10 p.Arg2111Trp Uncertain significance ★★ ⚠ same type
DNAH10 p.Arg2957Gln Uncertain significance ★★ same type
DNAH10 p.Arg3955His Uncertain significance ★★ ⚠ same type
DNAH10 p.Asp3319Gly Uncertain significance ★★ ⚠ same type
DNAH10 p.Glu4042Gln Uncertain significance ★★ ⚠ same type
DNAH10 p.Gly4445Glu Uncertain significance ★★ same type
DNAH10 p.Ile4202Thr 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/dnah10-p-ser228pro (accessed [today's date]).

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