Is ACSL1 p.Ala145Val (c.434C>T) pathogenic?

ACSL1 p.Ala145Val (c.434C>T) is classified Uncertain significance in ACSL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-17). AlphaMissense: likely benign (0.108); Absent from gnomAD v4.1.

How common is ACSL1 p.Ala145Val (c.434C>T) in the general population?

ACSL1 p.Ala145Val (c.434C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSL1 p.Ala145Val (c.434C>T)?

AlphaMissense predicts likely benign (score 0.108) — an in-silico prediction, not a clinical call.

ACSL1 p.Ala145Val

c.434C>T · rs2531687206 · VCV2454478

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.108 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,730)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.108	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -7.42	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 3.2	GERP 1.2, phastCons 0.4
Regional constraint	o/e 0.83	unconstrained · MANE · 46 kb · p 5.2e-07 · regional, not allelic
Overall
CADD	15.78	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

No allele count reported in gnomAD v4.1 (AN 1,613,730). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACSL1
Protein: p.Ala145Val
Coding: c.434C>T
MANE Select: NM_001995
dbSNP: rs2531687206
Type: single nucleotide variant
Location: chr4:184780375 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 90.16

Full ACSL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSL1 p.Arg376Gln Uncertain significance ★★ ⚠ same type
ACSL1 p.Gly506= Benign ★★ same type
ACSL1 p.Ala206Val Uncertain significance ★ ⚠ same type
ACSL1 p.Ala257Thr Uncertain significance ★ ⚠ same type
ACSL1 p.Ala435Thr Uncertain significance ★ ⚠ same type
ACSL1 p.Ala448Val Uncertain significance ★ ⚠ same type
ACSL1 p.Ala477Thr Uncertain significance ★ ⚠ same type
ACSL1 p.Ala482Thr 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/acsl1-p-ala145val (accessed [today's date]).

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