Is ACSF2 p.Ala234Val (c.701C>T) pathogenic?

ACSF2 p.Ala234Val (c.701C>T) is classified Uncertain significance in ACSF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-17). AlphaMissense: likely benign (0.1129); Ultra-rare (popmax 0.0293%, nfe).

How common is ACSF2 p.Ala234Val (c.701C>T) in the general population?

ACSF2 p.Ala234Val (c.701C>T) is ultra-rare (popmax 0.0293%, nfe) (gnomAD).

What do computational predictors say about ACSF2 p.Ala234Val (c.701C>T)?

AlphaMissense predicts likely benign (score 0.1129) — an in-silico prediction, not a clinical call.

ACSF2 p.Ala234Val

c.701C>T · rs199678954 · VCV2514415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1129 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0293%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1129	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -9.78	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 1.5	GERP 0.55, phastCons 0.8
Regional constraint	o/e 0.82	unconstrained · MANE · 48 kb · p 5.1e-07 · regional, not allelic
Overall
CADD	20.8	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 0.0293% European (non-Finnish) · 346/1,179,980 alleles

Filtering AF 0.0267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0257%

Overall 0.025% 404/1,613,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0485%	2,062
European (non-Finnish)grpmax	0.0293%	3,410
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Middle Eastern	0.0165%	6,062
African / African-American	0.00934%	10,709
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
Admixed American	0.00333%	30,002
South Asian	0.0022%	45,527

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala234Val
Coding: c.701C>T
MANE Select: NM_025149
dbSNP: rs199678954
Type: single nucleotide variant
Location: chr17:50462494 (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-ala234val (accessed [today's date]).

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