Is CYSRT1 p.Pro90Arg (c.269C>G) pathogenic?

CYSRT1 p.Pro90Arg (c.269C>G) is classified Uncertain significance in CYSRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-07). AlphaMissense: likely benign (0.1717); Very rare (popmax 0.00489%, eas).

How common is CYSRT1 p.Pro90Arg (c.269C>G) in the general population?

CYSRT1 p.Pro90Arg (c.269C>G) is very rare (popmax 0.00489%, eas) (gnomAD).

What do computational predictors say about CYSRT1 p.Pro90Arg (c.269C>G)?

AlphaMissense predicts likely benign (score 0.1717) — an in-silico prediction, not a clinical call.

CYSRT1 p.Pro90Arg

c.269C>G · rs1279489244 · VCV2558661

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1717 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00489%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1717	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -7.86	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 3.8	GERP -0.12, phastCons 0.88
Regional constraint	o/e 0.96	unconstrained · MANE · 431 bp · p 0.55 · regional, not allelic
Overall
CADD	19.71	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 0.00489% East Asian · 2/40,916 alleles

Filtering AF 0.00081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000303%

Overall 0.000129% 2/1,545,628 alleles · very rare exomes 2/1,393,256 · genomes 0/152,372 · 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: CYSRT1
Protein: p.Pro90Arg
Coding: c.269C>G
MANE Select: NM_199001
dbSNP: rs1279489244
Type: single nucleotide variant
Location: chr9:137225890 (GRCh38)
Gene constraint: LOEUF 1.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.71
Residue 90: the 'disordered' region

Full CYSRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYSRT1 p.Ala76Ser Uncertain significance ★ ⚠ same type
CYSRT1 p.Ala98Asp Uncertain significance ★ ⚠ same type
CYSRT1 p.Arg110His Uncertain significance ★ ⚠ same type
CYSRT1 p.Arg134Cys Uncertain significance ★ ⚠ same type
CYSRT1 p.Arg134His Uncertain significance ★ ⚠ same type
CYSRT1 p.Arg96His Uncertain significance ★ ⚠ same type
CYSRT1 p.Asp2Glu Uncertain significance ★ ⚠ same type
CYSRT1 p.Cys118Arg 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/cysrt1-p-pro90arg (accessed [today's date]).

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