Is ACSL5 p.Val474Met (c.1420G>A) pathogenic?

ACSL5 p.Val474Met (c.1420G>A) is classified Uncertain significance in ACSL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.2943); Very rare (popmax 0.00668%, eas).

How common is ACSL5 p.Val474Met (c.1420G>A) in the general population?

ACSL5 p.Val474Met (c.1420G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about ACSL5 p.Val474Met (c.1420G>A)?

AlphaMissense predicts likely benign (score 0.2943) — an in-silico prediction, not a clinical call.

ACSL5 p.Val474Met

c.1420G>A · VCV4000659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2943	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP -0.21, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.055 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 0.00668% East Asian · 3/44,884 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00105% 17/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
South Asian	0.0022%	45,540
Admixed American	0.00167%	59,998
African / African-American	0.00133%	74,920
European (non-Finnish)	0.000847%	118,006

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: ACSL5
Protein: p.Val474Met
Coding: c.1420G>A
MANE Select: NM_203379
Type: single nucleotide variant
Location: chr10:112421979 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.55

Full ACSL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSL5 p.Leu377= Benign ★★ same type
ACSL5 p.Pro40His Benign ★★ ⚠ same type
ACSL5 p.Thr486Ala Benign ★★ same type
ACSL5 c.-30+2050C>G Uncertain significance ★ same type
ACSL5 c.-30+2076C>A Uncertain significance ★ same type
ACSL5 c.-30+2100G>C Uncertain significance ★ same type
ACSL5 c.-30+2128C>T Uncertain significance ★ same type
ACSL5 c.-30+2164G>T 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/acsl5-p-val474met (accessed [today's date]).

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