Is ACSF3 p.Pro268Ser (c.802C>T) pathogenic?

ACSF3 p.Pro268Ser (c.802C>T) is classified Uncertain significance in ACSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). AlphaMissense: likely benign (0.1207); Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with ACSF3 p.Pro268Ser (c.802C>T)?

ACSF3 p.Pro268Ser (c.802C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACSF3 p.Pro268Ser (c.802C>T) in the general population?

ACSF3 p.Pro268Ser (c.802C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about ACSF3 p.Pro268Ser (c.802C>T)?

AlphaMissense predicts likely benign (score 0.1207) — an in-silico prediction, not a clinical call.

ACSF3 p.Pro268Ser

c.802C>T · rs748239351 · VCV2594198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1207 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1207	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.42, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 54 kb · p 2.3e-09 · regional, not allelic
Overall
CADD	22.7	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

Grpmax group 0.00668% East Asian · 3/44,884 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000434% 7/1,612,770 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
European (non-Finnish)	0.000339%	295,008

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.Pro268Ser
Coding: c.802C>T
MANE Select: NM_001243279
dbSNP: rs748239351
Type: single nucleotide variant
Location: chr16:89102739 (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.Pro268= Likely benign ★ same residue
ACSF3 p.Pro268fs Pathogenic/Likely pathogenic ★★ 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-pro268ser (accessed [today's date]).

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