Is ETFA p.Val63Leu (c.187G>T) pathogenic?

ETFA p.Val63Leu (c.187G>T) is classified Uncertain significance in ETFA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-01). AlphaMissense: ambiguous (0.4446); Absent from gnomAD v4.1.

How common is ETFA p.Val63Leu (c.187G>T) in the general population?

ETFA p.Val63Leu (c.187G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ETFA p.Val63Leu (c.187G>T)?

AlphaMissense predicts ambiguous (score 0.4446) — an in-silico prediction, not a clinical call.

ETFA p.Val63Leu

c.187G>T · rs2543032637 · VCV2582939

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4446 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4446	ambiguous
REVEL	0.455	indeterminate
SaProt	LLR -6.89	tolerated
Splicing
SpliceAI	Δ0.67	acceptor loss · deltas
Pangolin	Δ0.53	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 95 kb · p 0.0051 · regional, not allelic
Overall
CADD	23.1	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: ETFA
Protein: p.Val63Leu
Coding: c.187G>T
MANE Select: NM_000126
dbSNP: rs2543032637
Type: single nucleotide variant
Location: chr15:76292700 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.00 · 4 PDB
Residue 63: the 'domain i' region; an α-helix

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

Similar variants

MADD p.Ser63Ile Uncertain significance ★ ⚠ same residue
ETFA p.Val63= Likely benign ★ same residue
ETFA c.186+1G>A Likely pathogenic ★★ same type
ETFA c.39+1G>A Likely pathogenic ★★ same type
ETFA c.451+1G>A Likely pathogenic ★★ same type
ETFA c.452-2A>G Likely pathogenic ★★ same type
ETFA c.664+1G>A Likely pathogenic ★★ same type
ETFA c.665-1G>A 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/etfa-p-val63leu (accessed [today's date]).

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