Is CHD3 p.Ala3Val (c.8C>T) pathogenic?

CHD3 p.Ala3Val (c.8C>T) is classified Benign in CHD3 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-10-25). AlphaMissense: likely benign (0.1883); Common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CHD3-related disorder.

What condition is associated with CHD3 p.Ala3Val (c.8C>T)?

CHD3 p.Ala3Val (c.8C>T) is associated with CHD3-related disorder (ClinVar).

What do computational predictors say about CHD3 p.Ala3Val (c.8C>T)?

AlphaMissense predicts likely benign (score 0.1883) — an in-silico prediction, not a clinical call.

CHD3 p.Ala3Val

Q: How common is CHD3 p.Ala3Val (c.8C>T) in the general population?

CHD3 p.Ala3Val (c.8C>T) is common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.8C>T · rs931543 · VCV3055294

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1883 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CHD3-related disorder

Computational evidence

Protein change
AlphaMissense	0.1883	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,958 bp · p 0.95 · regional, not allelic
Overall
CADD	8.532	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 20.9% African / African-American · 15,679/74,972 alleles

Filtering AF 20.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.5%

Overall 3.54% 57,168/1,614,054 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	20.9%	5
Middle Eastern	8.55%	12
Finnishnot grpmax-eligible	7.98%	13
Admixed American	7.17%	14
Ashkenazi Jewishnot grpmax-eligible	4.18%	24
Remaining individualsnot grpmax-eligible	4.16%	24
East Asian	4.13%	24
Amishnot grpmax-eligible	2.87%	35
European (non-Finnish)	2.11%	47
South Asian	1.06%	95

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.Ala3Val
Coding: c.8C>T
MANE Select: NM_001005273
dbSNP: rs931543
Type: single nucleotide variant
Location: chr17:7889008 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 3: a UniProt-annotated variant site (in)

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

Disease context

CHD3-related disorder

Similar variants

CHD3 p.Ala3= Likely benign ★ same residue
CHD3 p.Ala3Glu Likely benign ★ same residue
CHD3 p.Arg1172Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1342Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg985Gln Pathogenic ★★ same condition
CHD3 p.Arg1491His Uncertain significance ★★ ⚠ same condition
CHD3 p.Arg684Ter Pathogenic ★ same condition
CHD3 p.Glu1653Ter 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/chd3-p-ala3val (accessed [today's date]).

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