Is CHDH p.Val119Glu (c.356T>A) pathogenic?

CHDH p.Val119Glu (c.356T>A) is classified Uncertain significance in CHDH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.1394); Very rare (popmax 0.00196%, amr).

How common is CHDH p.Val119Glu (c.356T>A) in the general population?

CHDH p.Val119Glu (c.356T>A) is very rare (popmax 0.00196%, amr) (gnomAD).

What do computational predictors say about CHDH p.Val119Glu (c.356T>A)?

AlphaMissense predicts likely benign (score 0.1394) — an in-silico prediction, not a clinical call.

CHDH p.Val119Glu

c.356T>A · rs1263572639 · VCV3144280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1394 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1394	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -6.54	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 2.2	GERP -3.8, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 6,228 bp · p 0.86 · regional, not allelic
Overall
CADD	11.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00196% Admixed American · 1/50,992 alleles

Overall 7.18e-05% 1/1,393,074 alleles · very rare

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: CHDH
Protein: p.Val119Glu
Coding: c.356T>A
MANE Select: NM_018397
dbSNP: rs1263572639
Type: single nucleotide variant
Location: chr3:53823653 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.84

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

Similar variants

CHDH p.Pro396Leu Uncertain significance ★★ ⚠ same type
CHDH c.704-3C>T Benign ★★ same type
CHDH p.Gly235= Benign ★★ same type
CHDH p.Val45= Benign ★★ same type
CHDH p.Ala13Val Uncertain significance ★ ⚠ same type
CHDH p.Ala170Thr Uncertain significance ★ ⚠ same type
CHDH p.Ala177Thr Uncertain significance ★ ⚠ same type
CHDH p.Ala240Val Uncertain significance ★ ⚠ 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/chdh-p-val119glu (accessed [today's date]).

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