Is CST11 p.Asp53Asn (c.157G>A) pathogenic?

CST11 p.Asp53Asn (c.157G>A) is classified Uncertain significance in CST11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). AlphaMissense: likely benign (0.0757); Very rare (popmax 0.00446%, eas).

How common is CST11 p.Asp53Asn (c.157G>A) in the general population?

CST11 p.Asp53Asn (c.157G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CST11 p.Asp53Asn (c.157G>A)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

CST11 p.Asp53Asn

c.157G>A · rs772748644 · VCV2456771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -7.90	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 -2.4	GERP -2.5
Regional constraint	o/e 1.13	unconstrained · MANE · 2,302 bp · p 0.096 · regional, not allelic
Overall
CADD	0.456	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 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00235% 38/1,613,800 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,442
European (non-Finnish)	0.00297%	33,711
South Asian	0.0011%	91,052

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: CST11
Protein: p.Asp53Asn
Coding: c.157G>A
MANE Select: NM_130794
dbSNP: rs772748644
Type: single nucleotide variant
Location: chr20:23452655 (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.Gln25Lys 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-asp53asn (accessed [today's date]).

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