Is CHD9 p.Val773Ile (c.2317G>A) pathogenic?

CHD9 p.Val773Ile (c.2317G>A) is classified Uncertain significance in CHD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.0776); Ultra-rare (popmax 0.0222%, sas).

How common is CHD9 p.Val773Ile (c.2317G>A) in the general population?

CHD9 p.Val773Ile (c.2317G>A) is ultra-rare (popmax 0.0222%, sas) (gnomAD).

What do computational predictors say about CHD9 p.Val773Ile (c.2317G>A)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

CHD9 p.Val773Ile

c.2317G>A · VCV4227936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0222%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 11 kb · p 0.00016 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0222% South Asian · 20/90,248 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0122%

Overall 0.00169% 27/1,600,508 alleles · ultra-rare exomes 21/1,448,276 · genomes 6/152,232 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0222%	4,512
African / African-American	0.0067%	14,934
East Asian	0.00224%	44,668
European (non-Finnish)	8.55e-05%	1,169,247

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: CHD9
Protein: p.Val773Ile
Coding: c.2317G>A
MANE Select: NM_001308319
Type: single nucleotide variant
Location: chr16:53231449 (GRCh38)
Gene constraint: LOEUF 0.309 · pLI 1.00 (gnomAD)
Residue 773: the chromo 2 domain

Full CHD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD9 p.Val773Ala Uncertain significance ★ same residue
CHD9 c.6620-2A>C Uncertain significance ★ same type
CHD9 p.Ala1363Thr Uncertain significance ★ ⚠ same type
CHD9 p.Ala1408Val Uncertain significance ★ ⚠ same type
CHD9 p.Ala1537Thr Uncertain significance ★ same type
CHD9 p.Ala167Val Uncertain significance ★ same type
CHD9 p.Ala1724Gly Uncertain significance ★ same type
CHD9 p.Ala1742Val 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/chd9-p-val773ile (accessed [today's date]).

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