Is SOAT2 p.Arg22His (c.65G>A) pathogenic?

SOAT2 p.Arg22His (c.65G>A) is classified Likely benign in SOAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely benign (0.0799); Rare (popmax 0.23%, afr).

How common is SOAT2 p.Arg22His (c.65G>A) in the general population?

SOAT2 p.Arg22His (c.65G>A) is rare (popmax 0.23%, afr) (gnomAD).

What do computational predictors say about SOAT2 p.Arg22His (c.65G>A)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

SOAT2 p.Arg22His

c.65G>A · VCV3321368

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.23%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.68	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 2.2	GERP -3.7, phastCons 0.001
Regional constraint	o/e 1.01	unconstrained · MANE · 21 kb · p 0.88 · regional, not allelic
Overall
CADD	6.498	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 0.23% African / African-American · 168/72,938 alleles

Filtering AF 0.202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.191%

Overall 0.0177% 273/1,539,456 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.23%	434
Remaining individualsnot grpmax-eligible	0.0134%	7,469
Admixed American	0.01%	9,955
European (non-Finnish)	0.00778%	12,853
Ashkenazi Jewishnot grpmax-eligible	0.00357%	27,980
East Asian	0.00245%	40,870
South Asian	0.0012%	83,032

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.Arg22His
Coding: c.65G>A
MANE Select: NM_003578
Type: single nucleotide variant
Location: chr12:53103642 (GRCh38)
Gene constraint: LOEUF 1.403 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.59 · 2 PDB
Residue 22: the 'disordered' region

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

Similar variants

ACAT2 p.Asn22Ser Uncertain significance ★ ⚠ same residue
ACAT2 p.Asn22Thr Uncertain significance ★ ⚠ same residue
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

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-arg22his (accessed [today's date]).

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