Is ACSF3 p.Pro375Thr (c.1123C>A) pathogenic?

ACSF3 p.Pro375Thr (c.1123C>A) is classified Uncertain significance in ACSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.1672); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACSF3 p.Pro375Thr (c.1123C>A)?

ACSF3 p.Pro375Thr (c.1123C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACSF3 p.Pro375Thr (c.1123C>A) in the general population?

ACSF3 p.Pro375Thr (c.1123C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSF3 p.Pro375Thr (c.1123C>A)?

AlphaMissense predicts likely benign (score 0.1672) — an in-silico prediction, not a clinical call.

ACSF3 p.Pro375Thr

c.1123C>A · rs1257930513 · VCV2287146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1672 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1672	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -11.36	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 7.2	GERP 1.6, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 54 kb · p 2.3e-09 · regional, not allelic
Overall
CADD	24.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACSF3
Protein: p.Pro375Thr
Coding: c.1123C>A
MANE Select: NM_001243279
dbSNP: rs1257930513
Type: single nucleotide variant
Location: chr16:89114484 (GRCh38)
Gene constraint: LOEUF 1.715 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.58

Full ACSF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACSF3 c.1366+3A>G Uncertain significance ★★ same condition
ACSF3 p.Ala15Asp Uncertain significance ★★ ⚠ same condition
ACSF3 p.Ala253Val Uncertain significance ★★ ⚠ same condition
ACSF3 p.Ala568Val Uncertain significance ★★ ⚠ same condition
ACSF3 p.Arg127Gly Uncertain significance ★★ ⚠ same condition
ACSF3 p.Arg208Lys Uncertain significance ★★ ⚠ same condition
ACSF3 p.Arg388Cys Uncertain significance ★★ ⚠ same condition
ACSF3 p.Arg39His Uncertain significance ★★ ⚠ same condition

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/acsf3-p-pro375thr (accessed [today's date]).

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