Is CHCHD3 p.Val182Phe (c.544G>T) pathogenic?

CHCHD3 p.Val182Phe (c.544G>T) is classified Uncertain significance in CHCHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: ambiguous (0.3435); Absent from gnomAD v4.1.

How common is CHCHD3 p.Val182Phe (c.544G>T) in the general population?

CHCHD3 p.Val182Phe (c.544G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHCHD3 p.Val182Phe (c.544G>T)?

AlphaMissense predicts ambiguous (score 0.3435) — an in-silico prediction, not a clinical call.

CHCHD3 p.Val182Phe

c.544G>T · VCV4653228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3435 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3435	ambiguous
REVEL	0.321	indeterminate
SaProt	LLR -12.41	damaging
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.38	GERP -3.7
Regional constraint	o/e 0.88	unconstrained · MANE · 296 kb · p 0.041 · regional, not allelic
Overall
CADD	22.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHCHD3
Protein: p.Val182Phe
Coding: c.544G>T
MANE Select: NM_017812
Type: single nucleotide variant
Location: chr7:132796558 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.73
Residue 182: the chch domain

Full CHCHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHCHD3 p.Ala120Thr Uncertain significance ★ ⚠ same type
CHCHD3 p.Ala124Ser Uncertain significance ★ ⚠ same type
CHCHD3 p.Ala167Ser Uncertain significance ★ ⚠ same type
CHCHD3 p.Ala52Val Uncertain significance ★ ⚠ same type
CHCHD3 p.Ala67Val Uncertain significance ★ ⚠ same type
CHCHD3 p.Arg117Cys Uncertain significance ★ ⚠ same type
CHCHD3 p.Arg117His Uncertain significance ★ ⚠ same type
CHCHD3 p.Arg132Gln 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/chchd3-p-val182phe (accessed [today's date]).

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