Is SI p.Pro1568= (c.4704C>T) pathogenic?

SI p.Pro1568= (c.4704C>T) is classified Benign in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). Ultra-rare (popmax 0.0384%, amr).

How common is SI p.Pro1568= (c.4704C>T) in the general population?

SI p.Pro1568= (c.4704C>T) is ultra-rare (popmax 0.0384%, amr) (gnomAD).

SI p.Pro1568=

c.4704C>T · rs376053398 · VCV1170820

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.9, phastCons 0.63
Overall
CADD	9.298	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% Admixed American · 23/59,848 alleles

Filtering AF 0.0262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0223%

Overall 0.00341% 55/1,610,578 alleles · ultra-rare exomes 43/1,458,824 · genomes 12/151,754 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0384%	2,602
Ashkenazi Jewishnot grpmax-eligible	0.0305%	3,275
South Asian	0.0044%	22,752
Remaining individualsnot grpmax-eligible	0.0016%	62,332
European (non-Finnish)	0.00144%	69,268
African / African-American	0.00134%	74,858

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: SI
Protein: p.Pro1568=
Coding: c.4704C>T
MANE Select: NM_001041
dbSNP: rs376053398
Type: single nucleotide variant
Location: chr3:164994394 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.86 · 2 PDB
Residue 1568: the 'sucrase' region

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

Similar variants

SI c.2426+1G>A Likely pathogenic ★★ same type
SI c.2737-2A>G Likely pathogenic ★★ same type
SI c.2893-1G>A Likely pathogenic ★★ same type
SI c.3099+1G>C Likely pathogenic ★★ same type
SI c.3521-1G>T Likely pathogenic ★★ same type
SI c.373+1G>A Likely pathogenic ★★ same type
SI c.4575+2T>C Likely pathogenic ★★ same type
SI c.4927-1G>A 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/si-p-pro1568 (accessed [today's date]).

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