Is CHD6 p.Ala151Val (c.452C>T) pathogenic?

CHD6 p.Ala151Val (c.452C>T) is classified Likely benign in CHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0667); Very rare (popmax 0.00167%, amr).

How common is CHD6 p.Ala151Val (c.452C>T) in the general population?

CHD6 p.Ala151Val (c.452C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CHD6 p.Ala151Val (c.452C>T)?

AlphaMissense predicts likely benign (score 0.0667) — an in-silico prediction, not a clinical call.

CHD6 p.Ala151Val

c.452C>T · rs745593837 · VCV2387227

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0667 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0667	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.5	phastCons 0.028
Regional constraint	o/e 0.96	unconstrained · MANE · 38 kb · p 0.49 · regional, not allelic
Overall
CADD	6.518	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,016 alleles · very rare exomes 3/1,461,834 · genomes 1/152,182 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
European (non-Finnish)	0.000254%	393,345

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: CHD6
Protein: p.Ala151Val
Coding: c.452C>T
MANE Select: NM_032221
dbSNP: rs745593837
Type: single nucleotide variant
Location: chr20:41533152 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)
Residue 151: the 'required for dna-dependent atpase activity' region; the 'disordered' region

Full CHD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD6 p.Ala151Glu Uncertain significance ★ ⚠ same residue
CHD6 p.Ala151Thr Benign ★ same residue
CHD6 c.1858-19G>A Benign ★★ same type
CHD6 c.554+5G>A Benign/Likely benign ★★ same type
CHD6 c.852+4T>C Benign ★★ same type
CHD6 p.Ala1205Gly Benign ★★ same type
CHD6 p.Arg2389Cys Benign ★★ same type
CHD6 p.Glu1271= Benign ★★ 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/chd6-p-ala151val (accessed [today's date]).

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