Is ACSF3 p.Val489Met (c.1465G>A) pathogenic?

ACSF3 p.Val489Met (c.1465G>A) is classified Uncertain significance in ACSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). AlphaMissense: ambiguous (0.392); Very rare (popmax 0.00178%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ACSF3 p.Val489Met (c.1465G>A)?

ACSF3 p.Val489Met (c.1465G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACSF3 p.Val489Met (c.1465G>A) in the general population?

ACSF3 p.Val489Met (c.1465G>A) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about ACSF3 p.Val489Met (c.1465G>A)?

AlphaMissense predicts ambiguous (score 0.392) — an in-silico prediction, not a clinical call.

ACSF3 p.Val489Met

c.1465G>A · VCV3825274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.392 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.392	ambiguous
REVEL	0.342	indeterminate
SaProt	LLR -12.07	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -2.7, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 54 kb · p 2.3e-09 · regional, not allelic
Overall
CADD	22.4	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

Grpmax group 0.00178% European (non-Finnish) · 21/1,180,036 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,614,094 alleles · very 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: ACSF3
Protein: p.Val489Met
Coding: c.1465G>A
MANE Select: NM_001243279
Type: single nucleotide variant
Location: chr16:89145365 (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 p.Val489Leu Uncertain significance ★ ⚠ same residue
ACSF3 p.Val489= Likely benign ★ same residue
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

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-val489met (accessed [today's date]).

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