Is ACSF3 p.Pro367Arg (c.1100C>G) pathogenic?

ACSF3 p.Pro367Arg (c.1100C>G) is classified Uncertain significance in ACSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). AlphaMissense: likely benign (0.1409); Ultra-rare (popmax 0.012%, afr); Associated with Inborn genetic diseases.

What condition is associated with ACSF3 p.Pro367Arg (c.1100C>G)?

ACSF3 p.Pro367Arg (c.1100C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ACSF3 p.Pro367Arg (c.1100C>G) in the general population?

ACSF3 p.Pro367Arg (c.1100C>G) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about ACSF3 p.Pro367Arg (c.1100C>G)?

AlphaMissense predicts likely benign (score 0.1409) — an in-silico prediction, not a clinical call.

ACSF3 p.Pro367Arg

c.1100C>G · rs151006784 · VCV2493386

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1409 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1409	likely benign
REVEL	0.392	indeterminate
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 54 kb · p 2.3e-09 · regional, not allelic
Overall
CADD	24.0	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 0.012% African / African-American · 9/74,924 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000558% 9/1,613,088 alleles · ultra-rare exomes 5/1,460,880 · genomes 4/152,208 · joint denominator

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.Pro367Arg
Coding: c.1100C>G
MANE Select: NM_001243279
dbSNP: rs151006784
Type: single nucleotide variant
Location: chr16:89114461 (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.Pro367= 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-pro367arg (accessed [today's date]).

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