Is CST11 p.Arg75Lys (c.224G>A) pathogenic?

CST11 p.Arg75Lys (c.224G>A) is classified Likely benign in CST11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-19). AlphaMissense: likely benign (0.0594); Absent from gnomAD v4.1.

How common is CST11 p.Arg75Lys (c.224G>A) in the general population?

CST11 p.Arg75Lys (c.224G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CST11 p.Arg75Lys (c.224G>A)?

AlphaMissense predicts likely benign (score 0.0594) — an in-silico prediction, not a clinical call.

CST11 p.Arg75Lys

c.224G>A · VCV3269954

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0594 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0594	likely benign
REVEL	0.004	strongly benign-leaning
SaProt	LLR -5.24	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 -1.1	GERP -2.5
Regional constraint	o/e 1.13	unconstrained · MANE · 2,302 bp · p 0.096 · regional, not allelic
Overall
CADD	0.005	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CST11
Protein: p.Arg75Lys
Coding: c.224G>A
MANE Select: NM_130794
Type: single nucleotide variant
Location: chr20:23452588 (GRCh38)
Gene constraint: LOEUF 1.415 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.03

Full CST11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST11 p.Ala21Pro Uncertain significance ★ ⚠ same type
CST11 p.Ala21Val Uncertain significance ★ ⚠ same type
CST11 p.Ala3Gly Uncertain significance ★ ⚠ same type
CST11 p.Arg66Ser Uncertain significance ★ ⚠ same type
CST11 p.Arg69Gln Uncertain significance ★ ⚠ same type
CST11 p.Asn114Asp Uncertain significance ★ ⚠ same type
CST11 p.Asp138Tyr Uncertain significance ★ ⚠ same type
CST11 p.Asp53Asn 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/cst11-p-arg75lys (accessed [today's date]).

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