Is CYSRT1 p.Thr61Ser (c.182C>G) pathogenic?

CYSRT1 p.Thr61Ser (c.182C>G) is classified Uncertain significance in CYSRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1075); Very rare (popmax 0.00793%, nfe).

How common is CYSRT1 p.Thr61Ser (c.182C>G) in the general population?

CYSRT1 p.Thr61Ser (c.182C>G) is very rare (popmax 0.00793%, nfe) (gnomAD).

What do computational predictors say about CYSRT1 p.Thr61Ser (c.182C>G)?

AlphaMissense predicts likely benign (score 0.1075) — an in-silico prediction, not a clinical call.

CYSRT1 p.Thr61Ser

c.182C>G · VCV4009095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00793%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1075	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -5.74	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 -0.2	GERP -2.4
Regional constraint	o/e 0.96	unconstrained · MANE · 431 bp · p 0.55 · regional, not allelic
Overall
CADD	5.437	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 0.00793% European (non-Finnish) · 91/1,146,896 alleles

Filtering AF 0.00658% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00609%

Overall 0.00594% 92/1,549,464 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00793%	12,603
Remaining individualsnot grpmax-eligible	0.00166%	60,064

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.Thr61Ser
Coding: c.182C>G
MANE Select: NM_199001
Type: single nucleotide variant
Location: chr9:137225803 (GRCh38)
Gene constraint: LOEUF 1.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.71
Residue 61: the 'disordered' region

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

Similar variants

CYSRT1 p.Thr61Asn Uncertain significance ★ ⚠ same residue
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

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-thr61ser (accessed [today's date]).

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