Is ETFB p.Val162Ala (c.485T>C) pathogenic?

ETFB p.Val162Ala (c.485T>C) is classified Uncertain significance in ETFB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: ambiguous (0.5327); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with ETFB p.Val162Ala (c.485T>C)?

ETFB p.Val162Ala (c.485T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ETFB p.Val162Ala (c.485T>C) in the general population?

ETFB p.Val162Ala (c.485T>C) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ETFB p.Val162Ala (c.485T>C)?

AlphaMissense predicts ambiguous (score 0.5327) — an in-silico prediction, not a clinical call.

ETFB p.Val162Ala

c.485T>C · VCV3510523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5327 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5327	ambiguous
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -11.21	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0022 · regional, not allelic
Overall
CADD	26.4	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

Grpmax group 0.004% African / African-American · 3/75,020 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00322% 52/1,613,304 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,007
European (non-Finnish)	0.00398%	25,101
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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: ETFB
Protein: p.Val162Ala
Coding: c.485T>C
MANE Select: NM_001985
Type: single nucleotide variant
Location: chr19:51347012 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 162: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ETFB p.Ala83Thr Uncertain significance ★★ ⚠ same condition
ETFB p.Arg174Cys Uncertain significance ★★ ⚠ same condition
ETFB p.Arg233Cys Uncertain significance ★★ ⚠ same condition
ETFB p.Arg254Gln Uncertain significance ★★ ⚠ same condition
ETFB p.Arg51Gln Uncertain significance ★★ ⚠ same condition
ETFB p.Arg76His Uncertain significance ★★ ⚠ same condition
ETFB p.Arg85Gln Uncertain significance ★★ ⚠ same condition
ETFB p.Asp118Gly Uncertain significance ★★ ⚠ same condition

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/etfb-p-val162ala (accessed [today's date]).

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