Is CHD7 p.Glu2012Val (c.6035A>T) pathogenic?

CHD7 p.Glu2012Val (c.6035A>T) is classified Likely pathogenic in CHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). AlphaMissense: ambiguous (0.4694); Absent from gnomAD v4.1; Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Glu2012Val (c.6035A>T)?

CHD7 p.Glu2012Val (c.6035A>T) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Glu2012Val (c.6035A>T) in the general population?

CHD7 p.Glu2012Val (c.6035A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD7 p.Glu2012Val (c.6035A>T)?

AlphaMissense predicts ambiguous (score 0.4694) — an in-silico prediction, not a clinical call.

CHD7 p.Glu2012Val

c.6035A>T · rs1805504949 · VCV1439188

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4694 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

CHARGE syndrome

Computational evidence

Protein change
AlphaMissense	0.4694	ambiguous
REVEL	0.664	pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP -2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 17 kb · p 7.3e-05 · regional, not allelic
Overall
CADD	23.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD7
Protein: p.Glu2012Val
Coding: c.6035A>T
MANE Select: NM_017780
dbSNP: rs1805504949
Type: single nucleotide variant
Location: chr8:60852638 (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 p.Glu2012Lys Conflicting classifications of pathogenicity ★ 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
CHD7 c.2957+2T>C 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-glu2012val (accessed [today's date]).

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