Is SOAT2 p.Ala205Pro (c.613G>C) pathogenic?

SOAT2 p.Ala205Pro (c.613G>C) is classified Uncertain significance in SOAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: ambiguous (0.3496); Ultra-rare (popmax 0.0214%, afr).

How common is SOAT2 p.Ala205Pro (c.613G>C) in the general population?

SOAT2 p.Ala205Pro (c.613G>C) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about SOAT2 p.Ala205Pro (c.613G>C)?

AlphaMissense predicts ambiguous (score 0.3496) — an in-silico prediction, not a clinical call.

SOAT2 p.Ala205Pro

c.613G>C · rs144833101 · VCV2373573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3496 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3496	ambiguous
REVEL	0.248	benign-leaning
SaProt	LLR -13.04	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.81, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 21 kb · p 0.88 · regional, not allelic
Overall
CADD	20.4	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 0.0214% African / African-American · 16/74,830 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00119% 19/1,591,092 alleles · ultra-rare exomes 14/1,438,708 · genomes 5/152,384 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,677
Remaining individualsnot grpmax-eligible	0.00324%	30,869
European (non-Finnish)	8.51e-05%	1,174,604

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: SOAT2
Protein: p.Ala205Pro
Coding: c.613G>C
MANE Select: NM_003578
dbSNP: rs144833101
Type: single nucleotide variant
Location: chr12:53115559 (GRCh38)
Gene constraint: LOEUF 1.403 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.59 · 2 PDB

Full SOAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SOAT2 p.Ala67= Benign ★★ same type
SOAT2 p.Leu402= Benign ★★ same type
ACAT2 p.Ala230Pro Uncertain significance ★ ⚠ same type
ACAT2 p.Ala323Gly Uncertain significance ★ ⚠ same type
ACAT2 p.Ala330Val Uncertain significance ★ ⚠ same type
ACAT2 p.Ala348Ser Uncertain significance ★ ⚠ same type
ACAT2 p.Ala357Gly Uncertain significance ★ ⚠ same type
ACAT2 p.Arg223His 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/soat2-p-ala205pro (accessed [today's date]).

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