Is CHD7 p.Pro2884Arg (c.8651C>G) pathogenic?

CHD7 p.Pro2884Arg (c.8651C>G) is classified Uncertain significance in CHD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.24); Ultra-rare (popmax 0.033%, mid).

How common is CHD7 p.Pro2884Arg (c.8651C>G) in the general population?

CHD7 p.Pro2884Arg (c.8651C>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CHD7 p.Pro2884Arg (c.8651C>G)?

AlphaMissense predicts likely benign (score 0.24) — an in-silico prediction, not a clinical call.

CHD7 p.Pro2884Arg

c.8651C>G · rs775800575 · VCV1302447

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.24 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.24	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 870 bp · p 0.43 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000124% 2/1,614,008 alleles · ultra-rare exomes 1/1,461,684 · genomes 1/152,324 · 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.Pro2884Arg
Coding: c.8651C>G
MANE Select: NM_017780
dbSNP: rs775800575
Type: single nucleotide variant
Location: chr8:60865590 (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

Similar variants

CHD7 p.Pro2884= Likely benign ★ same residue
CHD7 c.2097-2A>G Pathogenic ★★ same type
CHD7 c.2238+1G>A Pathogenic ★★ same type
CHD7 c.2377-1G>A Likely pathogenic ★★ same type
CHD7 c.2613+1G>A Pathogenic/Likely pathogenic ★★ same type
CHD7 c.2836-1G>A Pathogenic/Likely pathogenic ★★ same type
CHD7 c.2836-2A>T Pathogenic ★★ same type
CHD7 c.2957+2T>C Pathogenic ★★ same type

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-pro2884arg (accessed [today's date]).

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