Is ACSF2 p.Met161Val (c.481A>G) pathogenic?

ACSF2 p.Met161Val (c.481A>G) is classified Uncertain significance in ACSF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0605); Rare (popmax 0.308%, afr).

How common is ACSF2 p.Met161Val (c.481A>G) in the general population?

ACSF2 p.Met161Val (c.481A>G) is rare (popmax 0.308%, afr) (gnomAD).

What do computational predictors say about ACSF2 p.Met161Val (c.481A>G)?

AlphaMissense predicts likely benign (score 0.0605) — an in-silico prediction, not a clinical call.

ACSF2 p.Met161Val

c.481A>G · VCV4218693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0605 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.308%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0605	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -6.88	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 -0.98	GERP -2
Regional constraint	o/e 0.82	unconstrained · MANE · 48 kb · p 5.1e-07 · regional, not allelic
Overall
CADD	2.144	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 0.308% African / African-American · 231/75,028 alleles

Filtering AF 0.275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.263%

Overall 0.0152% 245/1,614,088 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.308%	325
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Admixed American	0.005%	20,007

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: ACSF2
Protein: p.Met161Val
Coding: c.481A>G
MANE Select: NM_025149
Type: single nucleotide variant
Location: chr17:50461660 (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-met161val (accessed [today's date]).

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