Is CYSRT1 p.Pro130Ser (c.388C>T) pathogenic?

CYSRT1 p.Pro130Ser (c.388C>T) is classified Uncertain significance in CYSRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-25). AlphaMissense: ambiguous (0.4835); Very rare (popmax 0.00137%, afr).

How common is CYSRT1 p.Pro130Ser (c.388C>T) in the general population?

CYSRT1 p.Pro130Ser (c.388C>T) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about CYSRT1 p.Pro130Ser (c.388C>T)?

AlphaMissense predicts ambiguous (score 0.4835) — an in-silico prediction, not a clinical call.

CYSRT1 p.Pro130Ser

c.388C>T · VCV3838041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Computational evidence

Protein change
AlphaMissense	0.4835	ambiguous
REVEL	0.341	indeterminate
SaProt	LLR -6.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 431 bp · p 0.55 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/73,166 alleles

Filtering AF 0.000128% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000501% 7/1,396,818 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00167%	60,034
African / African-Americangrpmax	0.00137%	73,166
European (non-Finnish)	0.000436%	229,361

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro130Ser
Coding: c.388C>T
MANE Select: NM_199001
Type: single nucleotide variant
Location: chr9:137226009 (GRCh38)
Gene constraint: LOEUF 1.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.71

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-pro130ser (accessed [today's date]).

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