Is CHD7 p.Ala2132= (c.6396T>C) pathogenic?

CHD7 p.Ala2132= (c.6396T>C) is classified Likely benign in CHD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-01). Very rare (popmax 0.0011%, nfe); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Ala2132= (c.6396T>C)?

CHD7 p.Ala2132= (c.6396T>C) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Ala2132= (c.6396T>C) in the general population?

CHD7 p.Ala2132= (c.6396T>C) is very rare (popmax 0.0011%, nfe) (gnomAD).

CHD7 p.Ala2132=

c.6396T>C · rs763720460 · VCV1623105

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

CHARGE syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.85	GERP -3.9, phastCons 0.007
Overall
CADD	5.748	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,886 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000806% 13/1,613,726 alleles · very rare exomes 12/1,461,656 · genomes 1/152,070 · 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.Ala2132=
Coding: c.6396T>C
MANE Select: NM_017780
dbSNP: rs763720460
Type: single nucleotide variant
Location: chr8:60853121 (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.Ala2132Pro Uncertain significance ★ same residue
CHD7 p.Ala2132Thr 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-ala2132 (accessed [today's date]).

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