Is SF1 p.Pro522= (c.1566C>T) pathogenic?

SF1 p.Pro522= (c.1566C>T) is classified Likely benign in SF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). Very rare (popmax 0.00378%, sas).

How common is SF1 p.Pro522= (c.1566C>T) in the general population?

SF1 p.Pro522= (c.1566C>T) is very rare (popmax 0.00378%, sas) (gnomAD).

SF1 p.Pro522=

c.1566C>T · VCV3317811

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00378%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.157	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 0.4, phastCons 1
Overall
CADD	9.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00378% South Asian · 2/52,878 alleles

Filtering AF 0.000627% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000235%

Overall 0.000488% 6/1,229,426 alleles · very rare exomes 5/1,087,608 · genomes 1/141,818 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00378%	26,439
European (non-Finnish)	0.000416%	240,488

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.Pro522=
Coding: c.1566C>T
MANE Select: NM_004630
Type: single nucleotide variant
Location: chr11:64766916 (GRCh38)
Gene constraint: LOEUF 0.22 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.28 · 10 PDB
Residue 522: 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-pro522 (accessed [today's date]).

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