Is ACSL5 p.Pro35Thr (c.103C>A) pathogenic?

ACSL5 p.Pro35Thr (c.103C>A) is classified Uncertain significance in ACSL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). AlphaMissense: likely benign (0.1969); Ultra-rare (popmax 0.0214%, afr).

How common is ACSL5 p.Pro35Thr (c.103C>A) in the general population?

ACSL5 p.Pro35Thr (c.103C>A) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about ACSL5 p.Pro35Thr (c.103C>A)?

AlphaMissense predicts likely benign (score 0.1969) — an in-silico prediction, not a clinical call.

ACSL5 p.Pro35Thr

c.103C>A · VCV4000635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1969 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1969	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -11.98	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.055 · regional, not allelic
Overall
CADD	24.9	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 0.0214% African / African-American · 16/74,898 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.000991% 16/1,613,958 alleles · ultra-rare

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.Pro35Thr
Coding: c.103C>A
MANE Select: NM_203379
Type: single nucleotide variant
Location: chr10:112395049 (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-pro35thr (accessed [today's date]).

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