Is ACSL1 p.Ser196Pro (c.586T>C) pathogenic?

ACSL1 p.Ser196Pro (c.586T>C) is classified Uncertain significance in ACSL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely benign (0.1258); Ultra-rare (popmax 0.0107%, afr).

How common is ACSL1 p.Ser196Pro (c.586T>C) in the general population?

ACSL1 p.Ser196Pro (c.586T>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about ACSL1 p.Ser196Pro (c.586T>C)?

AlphaMissense predicts likely benign (score 0.1258) — an in-silico prediction, not a clinical call.

ACSL1 p.Ser196Pro

c.586T>C · VCV3482394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1258 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1258	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -7.06	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 0.92	GERP 0.76, phastCons 0.022
Regional constraint	o/e 0.83	unconstrained · MANE · 46 kb · p 5.2e-07 · regional, not allelic
Overall
CADD	20.1	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

Grpmax group 0.0107% African / African-American · 8/74,914 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000621% 10/1,610,668 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,364
Admixed American	0.00334%	29,966

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: ACSL1
Protein: p.Ser196Pro
Coding: c.586T>C
MANE Select: NM_001995
Type: single nucleotide variant
Location: chr4:184776654 (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.Ala145Val Uncertain significance ★ ⚠ 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

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-ser196pro (accessed [today's date]).

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