Is DNAH9 p.Met583Val (c.1747A>G) pathogenic?

DNAH9 p.Met583Val (c.1747A>G) is classified Benign/Likely benign in DNAH9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0722); Low-frequency (popmax 1.1%, sas).

How common is DNAH9 p.Met583Val (c.1747A>G) in the general population?

DNAH9 p.Met583Val (c.1747A>G) is low-frequency (popmax 1.1%, sas) (gnomAD).

What do computational predictors say about DNAH9 p.Met583Val (c.1747A>G)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

DNAH9 p.Met583Val

c.1747A>G · rs534432763 · VCV1585019

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.1%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.077	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 0.3	GERP -3.6
Regional constraint	o/e 0.95	unconstrained · MANE · 333 kb · p 0.00016 · regional, not allelic
Overall
CADD	1.603	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 1.1% South Asian · 998/91,074 alleles

Filtering AF 1.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.02%

Overall 0.0652% 1,052/1,614,144 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.1%	91
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0688%	1,454
African / African-American	0.004%	25,018
European (non-Finnish)	0.000254%	393,324

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.Met583Val
Coding: c.1747A>G
MANE Select: NM_001372
dbSNP: rs534432763
Type: single nucleotide variant
Location: chr17:11636745 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 583: the 'stem' region

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

Similar variants

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
DNAH9 p.Arg1517Ter 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-met583val (accessed [today's date]).

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