Is CHD7 p.Asp880Val (c.2639A>T) pathogenic?

CHD7 p.Asp880Val (c.2639A>T) is classified Likely benign in CHD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-01). AlphaMissense: likely pathogenic (0.9576); Ultra-rare (popmax 0.0166%, sas); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Asp880Val (c.2639A>T)?

CHD7 p.Asp880Val (c.2639A>T) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Asp880Val (c.2639A>T) in the general population?

CHD7 p.Asp880Val (c.2639A>T) is ultra-rare (popmax 0.0166%, sas) (gnomAD).

What do computational predictors say about CHD7 p.Asp880Val (c.2639A>T)?

AlphaMissense predicts likely pathogenic (score 0.9576) — an in-silico prediction, not a clinical call.

CHD7 p.Asp880Val

c.2639A>T · VCV3716923

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9576 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, sas)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

CHARGE syndrome

Computational evidence

Protein change
AlphaMissense	0.9576	likely pathogenic
REVEL	0.824	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 21 kb · p 5.2e-06 · regional, not allelic
Overall
CADD	28.2	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 0.0166% South Asian · 15/90,110 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00829%

Overall 0.000933% 15/1,607,548 alleles · ultra-rare exomes 15/1,458,272 · genomes 0/149,276 · joint denominator

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.Asp880Val
Coding: c.2639A>T
MANE Select: NM_017780
Type: single nucleotide variant
Location: chr8:60820032 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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 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
CHD7 c.2957+2T>C Pathogenic ★★ same condition
CHD7 c.3202-3T>G Pathogenic/Likely 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-asp880val (accessed [today's date]).

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