Is CHD3 p.Arg271Trp (c.811C>T) pathogenic?

CHD3 p.Arg271Trp (c.811C>T) is classified Likely benign in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-14). AlphaMissense: likely pathogenic (0.6433); Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Arg271Trp (c.811C>T)?

CHD3 p.Arg271Trp (c.811C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHD3 p.Arg271Trp (c.811C>T) in the general population?

CHD3 p.Arg271Trp (c.811C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CHD3 p.Arg271Trp (c.811C>T)?

AlphaMissense predicts likely pathogenic (score 0.6433) — an in-silico prediction, not a clinical call.

CHD3 p.Arg271Trp

c.811C>T · VCV3832786

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6433 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6433	likely pathogenic
REVEL	0.556	indeterminate
SaProt	LLR -11.18	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.74, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 829 bp · p 0.013 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,878 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.0013% 21/1,613,886 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
South Asian	0.0022%	45,535
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.0011%	90,770

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: CHD3
Protein: p.Arg271Trp
Coding: c.811C>T
MANE Select: NM_001005273
Type: single nucleotide variant
Location: chr17:7893822 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 271: the 'disordered' region

Full CHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD3 p.Arg271Leu Uncertain significance ★ ⚠ same residue
CHD3 p.Arg103Ter Pathogenic ★★ same condition
CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg966Trp Pathogenic ★★ ⚠ same condition
CHD3 p.Arg985Trp Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Pro1918= Likely pathogenic ★★ same condition
CHD3 p.Arg1266Trp Uncertain significance ★★ ⚠ same condition
CHD3 p.Arg1377Cys Uncertain significance ★★ ⚠ 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/chd3-p-arg271trp (accessed [today's date]).

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