Is CHD7 p.Ala950Val (c.2849C>T) pathogenic?

CHD7 p.Ala950Val (c.2849C>T) is classified Uncertain significance in CHD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-10). AlphaMissense: likely benign (0.1217); Very rare (popmax 0.00017%, nfe); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Ala950Val (c.2849C>T)?

CHD7 p.Ala950Val (c.2849C>T) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Ala950Val (c.2849C>T) in the general population?

CHD7 p.Ala950Val (c.2849C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CHD7 p.Ala950Val (c.2849C>T)?

AlphaMissense predicts likely benign (score 0.1217) — an in-silico prediction, not a clinical call.

CHD7 p.Ala950Val

c.2849C>T · rs2487806970 · VCV2905178

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1217 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

CHARGE syndrome

Computational evidence

Protein change
AlphaMissense	0.1217	likely benign
REVEL	0.519	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 21 kb · p 5.2e-06 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,762 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,550 alleles · very rare

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: CHD7
Protein: p.Ala950Val
Coding: c.2849C>T
MANE Select: NM_017780
dbSNP: rs2487806970
Type: single nucleotide variant
Location: chr8:60822037 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 950: the 'disordered' region

Full CHD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CHARGE syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD7 p.Ala950Thr Benign/Likely benign ★★ same residue
CHD7 p.Ala950= Likely benign ★ same residue
CHD7 c.2097-2A>G Pathogenic ★★ same condition
CHD7 c.2238+1G>A Pathogenic ★★ same condition
CHD7 c.2377-1G>A Likely pathogenic ★★ same condition
CHD7 c.2613+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD7 c.2836-1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD7 c.2836-2A>T Pathogenic ★★ same condition

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/chd7-p-ala950val (accessed [today's date]).

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