Is SOAT1 p.Phe263Ser (c.788T>C) pathogenic?

SOAT1 p.Phe263Ser (c.788T>C) is classified Uncertain significance in SOAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely pathogenic (0.6681); Very rare (popmax 0.00446%, eas).

How common is SOAT1 p.Phe263Ser (c.788T>C) in the general population?

SOAT1 p.Phe263Ser (c.788T>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about SOAT1 p.Phe263Ser (c.788T>C)?

AlphaMissense predicts likely pathogenic (score 0.6681) — an in-silico prediction, not a clinical call.

SOAT1 p.Phe263Ser

c.788T>C · VCV3321365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6681	likely pathogenic
REVEL	0.361	indeterminate
SaProt	LLR -13.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 51 kb · p 0.00056 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00446% East Asian · 2/44,854 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000137% 2/1,461,514 alleles · very rare

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: SOAT1
Protein: p.Phe263Ser
Coding: c.788T>C
MANE Select: NM_003101
Type: single nucleotide variant
Location: chr1:179342121 (GRCh38)
Gene constraint: LOEUF 0.988 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.22 · 5 PDB
Residue 263: an α-helix

Full SOAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAT1 p.Lys263Ter Pathogenic/Likely pathogenic ★★ same residue
ACAT1 c.1006-1G>A Pathogenic ★★ same type
ACAT1 c.1006-1G>C Pathogenic ★★ same type
ACAT1 c.1006-2A>C Pathogenic ★★ same type
ACAT1 c.1163+2T>C Pathogenic ★★ same type
ACAT1 c.120+1G>C Likely pathogenic ★★ same type
ACAT1 c.121-3C>G Pathogenic/Likely pathogenic ★★ same type
ACAT1 c.238+2T>A Pathogenic/Likely pathogenic ★★ 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/soat1-p-phe263ser (accessed [today's date]).

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