Is SF1 p.Pro367Ser (c.1099C>T) pathogenic?

SF1 p.Pro367Ser (c.1099C>T) is classified Uncertain significance in SF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: likely benign (0.27); Ultra-rare (popmax 0.0134%, eas).

How common is SF1 p.Pro367Ser (c.1099C>T) in the general population?

SF1 p.Pro367Ser (c.1099C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about SF1 p.Pro367Ser (c.1099C>T)?

AlphaMissense predicts likely benign (score 0.27) — an in-silico prediction, not a clinical call.

SF1 p.Pro367Ser

c.1099C>T · rs775788655 · VCV3160782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.27 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.27	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -8.32	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,358 bp · p 0.046 · regional, not allelic
Overall
CADD	26.3	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 0.0134% East Asian · 6/44,892 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000372% 6/1,613,654 alleles · ultra-rare exomes 4/1,461,434 · genomes 2/152,220 · 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: SF1
Protein: p.Pro367Ser
Coding: c.1099C>T
MANE Select: NM_004630
dbSNP: rs775788655
Type: single nucleotide variant
Location: chr11:64767814 (GRCh38)
Gene constraint: LOEUF 0.22 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.28 · 10 PDB
Residue 367: the 'disordered' region

Full SF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SF1 c.31+105G>A Uncertain significance ★ same type
SF1 c.31+111C>G Uncertain significance ★ same type
SF1 c.31+112C>T Uncertain significance ★ same type
SF1 c.31+123C>T Uncertain significance ★ same type
SF1 c.31+12C>A Uncertain significance ★ same type
SF1 c.31+138G>A Uncertain significance ★ same type
SF1 c.31+139G>C Uncertain significance ★ same type
SF1 c.31+141G>A 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/sf1-p-pro367ser (accessed [today's date]).

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