Is ACSF2 p.Arg12Thr (c.35G>C) pathogenic?

ACSF2 p.Arg12Thr (c.35G>C) is classified Uncertain significance in ACSF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely benign (0.1813); Absent from gnomAD v4.1.

How common is ACSF2 p.Arg12Thr (c.35G>C) in the general population?

ACSF2 p.Arg12Thr (c.35G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSF2 p.Arg12Thr (c.35G>C)?

AlphaMissense predicts likely benign (score 0.1813) — an in-silico prediction, not a clinical call.

ACSF2 p.Arg12Thr

c.35G>C · VCV3482205

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1813 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1813	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -8.64	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 2.3	GERP -3, phastCons 0.99
Regional constraint	o/e 0.82	unconstrained · MANE · 48 kb · p 5.1e-07 · regional, not allelic
Overall
CADD	18.7	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

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: ACSF2
Protein: p.Arg12Thr
Coding: c.35G>C
MANE Select: NM_025149
Type: single nucleotide variant
Location: chr17:50426296 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.40

Full ACSF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHAD p.Leu226= Benign ★★ same type
CHAD p.Pro349= Benign ★★ same type
CHAD p.Thr350Ile Benign ★★ ⚠ same type
ACSF2 p.Ala112Ser Uncertain significance ★ ⚠ same type
ACSF2 p.Ala15Pro Uncertain significance ★ ⚠ same type
ACSF2 p.Ala15Thr Uncertain significance ★ ⚠ same type
ACSF2 p.Ala160Pro Uncertain significance ★ ⚠ same type
ACSF2 p.Ala160Val 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/acsf2-p-arg12thr (accessed [today's date]).

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