Is CYRIB p.Ser31Pro (c.91T>C) pathogenic?

CYRIB p.Ser31Pro (c.91T>C) is classified Uncertain significance in CYRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.1892); Very rare (popmax 0.00448%, sas).

How common is CYRIB p.Ser31Pro (c.91T>C) in the general population?

CYRIB p.Ser31Pro (c.91T>C) is very rare (popmax 0.00448%, sas) (gnomAD).

What do computational predictors say about CYRIB p.Ser31Pro (c.91T>C)?

AlphaMissense predicts likely benign (score 0.1892) — an in-silico prediction, not a clinical call.

CYRIB p.Ser31Pro

c.91T>C · rs751308047 · VCV3079789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1892 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00448%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1892	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -8.91	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 9.4	GERP 1, phastCons 1
Overall
CADD	23.7	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 0.00448% South Asian · 4/89,262 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000905%

Overall 0.000275% 4/1,456,846 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: CYRIB
Protein: p.Ser31Pro
Coding: c.91T>C
MANE Select: NM_001353258
dbSNP: rs751308047
Type: single nucleotide variant
Location: chr8:129871479 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 1 PDB

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

Similar variants

CYRIB p.Arg105Gly Uncertain significance ★ ⚠ same type
CYRIB p.Arg105Ser Uncertain significance ★ ⚠ same type
CYRIB p.Arg124Gln Uncertain significance ★ ⚠ same type
CYRIB p.Gly175Arg Uncertain significance ★ ⚠ same type
CYRIB p.Pro70Ala Uncertain significance ★ same type
CYRIB p.Thr112Ala Uncertain significance ★ ⚠ same type
CYRIB p.Thr29Ala Uncertain significance ★ ⚠ same type
CYRIB p.Trp80Arg 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/cyrib-p-ser31pro (accessed [today's date]).

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