Is CHD7 p.Pro2743Arg (c.8228C>G) pathogenic?

CHD7 p.Pro2743Arg (c.8228C>G) is classified Uncertain significance in CHD7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-21). AlphaMissense: likely pathogenic (0.8555); Very rare (popmax 0.00223%, eas); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Pro2743Arg (c.8228C>G)?

CHD7 p.Pro2743Arg (c.8228C>G) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Pro2743Arg (c.8228C>G) in the general population?

CHD7 p.Pro2743Arg (c.8228C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CHD7 p.Pro2743Arg (c.8228C>G)?

AlphaMissense predicts likely pathogenic (score 0.8555) — an in-silico prediction, not a clinical call.

CHD7 p.Pro2743Arg

c.8228C>G · rs1806181529 · VCV2185518

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

CHARGE syndrome

Computational evidence

Protein change
AlphaMissense	0.8555	likely pathogenic
REVEL	0.736	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 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 870 bp · p 0.43 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,842 alleles

Overall 6.2e-05% 1/1,612,218 alleles · very rare exomes 0/1,459,844 · genomes 1/152,374 · 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.Pro2743Arg
Coding: c.8228C>G
MANE Select: NM_017780
dbSNP: rs1806181529
Type: single nucleotide variant
Location: chr8:60865167 (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-pro2743arg (accessed [today's date]).

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