Is CHD4 p.Ala13Val (c.38C>T) pathogenic?

CHD4 p.Ala13Val (c.38C>T) is classified Benign in CHD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1214); Ultra-rare (popmax 0.0322%, afr).

How common is CHD4 p.Ala13Val (c.38C>T) in the general population?

CHD4 p.Ala13Val (c.38C>T) is ultra-rare (popmax 0.0322%, afr) (gnomAD).

What do computational predictors say about CHD4 p.Ala13Val (c.38C>T)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

CHD4 p.Ala13Val

c.38C>T · VCV3712422

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0322%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -5.89	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 7.2	GERP 1, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 4,403 bp · p 0.0078 · regional, not allelic
Overall
CADD	25.9	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 0.0322% African / African-American · 23/71,398 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0186%

Overall 0.00178% 28/1,569,380 alleles · ultra-rare exomes 17/1,417,052 · genomes 11/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0322%	3,104
European (non-Finnish)	0.000431%	232,120

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: CHD4
Protein: p.Ala13Val
Coding: c.38C>T
MANE Select: NM_001273
Type: single nucleotide variant
Location: chr12:6606336 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.41 · 12 PDB
Residue 13: the 'disordered' region

Full CHD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD4 p.Ala13= Likely benign ★ same residue
CHD4 p.Arg1068His Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1173Gln Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1173Trp Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1177Cys Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1177His Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1183Cys Pathogenic/Likely pathogenic ★★ same type
CHD4 p.Arg1183His Pathogenic/Likely 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/chd4-p-ala13val (accessed [today's date]).

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