Is DNAH9 p.Pro70Ser (c.208C>T) pathogenic?

DNAH9 p.Pro70Ser (c.208C>T) is classified Benign in DNAH9 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1605); Common (popmax 5.44%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DNAH9 p.Pro70Ser (c.208C>T)?

AlphaMissense predicts likely benign (score 0.1605) — an in-silico prediction, not a clinical call.

DNAH9 p.Pro70Ser

Q: How common is DNAH9 p.Pro70Ser (c.208C>T) in the general population?

DNAH9 p.Pro70Ser (c.208C>T) is common (popmax 5.44%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.208C>T · rs28570215 · VCV1294645

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1605 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.44%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1605	likely benign
REVEL	0.063	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 2.1	GERP 1.9, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 34 kb · p 0.0046 · regional, not allelic
Overall
CADD	20.3	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 5.44% African / African-American · 3,547/65,174 alleles

Filtering AF 5.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.23%

Overall 0.281% 3,859/1,373,036 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.44%	18
Admixed American	0.406%	246
Remaining individualsnot grpmax-eligible	0.312%	320
Middle Eastern	0.129%	774
European (non-Finnish)	0.00318%	31,470
South Asian	0.00165%	60,712

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: DNAH9
Protein: p.Pro70Ser
Coding: c.208C>T
MANE Select: NM_001372
dbSNP: rs28570215
Type: single nucleotide variant
Location: chr17:11598706 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 70: the 'stem' region

Full DNAH9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH9 p.Pro70Leu Uncertain significance ⚠ same residue
DNAH9 c.11406+1G>T Likely pathogenic ★★ same type
DNAH9 c.1901+1G>A Likely pathogenic ★★ same type
DNAH9 c.2928+1G>A Likely pathogenic ★★ same type
DNAH9 c.5709+1G>T Likely pathogenic ★★ same type
DNAH9 c.615-2A>G Likely pathogenic ★★ same type
DNAH9 c.6847+1G>A Likely pathogenic ★★ same type
DNAH9 p.Arg1344Ter Pathogenic/Likely pathogenic ★★ 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/dnah9-p-pro70ser (accessed [today's date]).

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