Is ACSF3 p.Ala545Val (c.1634C>T) pathogenic?

ACSF3 p.Ala545Val (c.1634C>T) is classified Uncertain significance in ACSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-01). AlphaMissense: likely benign (0.1668); Very rare (popmax 0.00501%, amr); Associated with Inborn genetic diseases.

What condition is associated with ACSF3 p.Ala545Val (c.1634C>T)?

ACSF3 p.Ala545Val (c.1634C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACSF3 p.Ala545Val (c.1634C>T) in the general population?

ACSF3 p.Ala545Val (c.1634C>T) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about ACSF3 p.Ala545Val (c.1634C>T)?

AlphaMissense predicts likely benign (score 0.1668) — an in-silico prediction, not a clinical call.

ACSF3 p.Ala545Val

c.1634C>T · VCV3482294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1668 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1668	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -8.70	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 5.7	GERP 1.2, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 54 kb · p 2.3e-09 · regional, not allelic
Overall
CADD	17.81	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 0.00501% Admixed American · 3/59,902 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000616% 9/1,460,774 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,967
European (non-Finnish)	0.000509%	196,603

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.Ala545Val
Coding: c.1634C>T
MANE Select: NM_001243279
Type: single nucleotide variant
Location: chr16:89154110 (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.Ala545= 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
ACSF3 p.Arg388Cys 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-ala545val (accessed [today's date]).

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