Is CHD1L p.Val366Phe (c.1096G>T) pathogenic?

CHD1L p.Val366Phe (c.1096G>T) is classified Uncertain significance in CHD1L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-02). AlphaMissense: likely pathogenic (0.7607); Very rare (popmax 0.000254%, nfe).

How common is CHD1L p.Val366Phe (c.1096G>T) in the general population?

CHD1L p.Val366Phe (c.1096G>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CHD1L p.Val366Phe (c.1096G>T)?

AlphaMissense predicts likely pathogenic (score 0.7607) — an in-silico prediction, not a clinical call.

CHD1L p.Val366Phe

c.1096G>T · VCV4653265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7607	likely pathogenic
REVEL	0.859	moderately pathogenic-leaning
SaProt	LLR -14.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.6, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 53 kb · p 0.0005 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,932 alleles

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

Overall 0.000186% 3/1,613,812 alleles · very rare exomes 1/1,461,738 · genomes 2/152,074 · 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: CHD1L
Protein: p.Val366Phe
Coding: c.1096G>T
MANE Select: NM_004284
Type: single nucleotide variant
Location: chr1:147270942 (GRCh38)
Gene constraint: LOEUF 1.152 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.81 · 7 PDB
Residue 366: the helicase c-terminal domain; a β-strand

Full CHD1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD1L p.Val366Ala Uncertain significance ★ ⚠ same residue
CHD1L p.Arg236His Uncertain significance ★★ ⚠ same type
CHD1L p.Gln12Arg Uncertain significance ★★ ⚠ same type
CHD1L p.Gln594Pro Uncertain significance ★★ same type
CHD1L p.Pro727Thr Uncertain significance ★★ ⚠ same type
CHD1L p.Thr629Asn Uncertain significance ★★ ⚠ same type
CHD1L p.Val896Met Uncertain significance ★★ ⚠ same type
CHD1L c.1085+39= 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/chd1l-p-val366phe (accessed [today's date]).

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