Is ACSL5 p.Ser68Thr (c.203G>C) pathogenic?

ACSL5 p.Ser68Thr (c.203G>C) is classified Uncertain significance in ACSL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-14). AlphaMissense: likely benign (0.0727); Very rare (popmax 0.00525%, nfe).

How common is ACSL5 p.Ser68Thr (c.203G>C) in the general population?

ACSL5 p.Ser68Thr (c.203G>C) is very rare (popmax 0.00525%, nfe) (gnomAD).

What do computational predictors say about ACSL5 p.Ser68Thr (c.203G>C)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

ACSL5 p.Ser68Thr

c.203G>C · rs746731885 · VCV2496107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00525%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -4.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.7	GERP -4.9
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.055 · regional, not allelic
Overall
CADD	0.068	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 0.00525% European (non-Finnish) · 62/1,180,012 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00403% 65/1,613,996 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00525%	19,032
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00133%	74,918

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.Ser68Thr
Coding: c.203G>C
MANE Select: NM_203379
dbSNP: rs746731885
Type: single nucleotide variant
Location: chr10:112398947 (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-ser68thr (accessed [today's date]).

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