Is CST11 p.Ile67Phe (c.199A>T) pathogenic?

CST11 p.Ile67Phe (c.199A>T) is classified Uncertain significance in CST11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.2855); Ultra-rare (popmax 0.0174%, afr).

How common is CST11 p.Ile67Phe (c.199A>T) in the general population?

CST11 p.Ile67Phe (c.199A>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about CST11 p.Ile67Phe (c.199A>T)?

AlphaMissense predicts likely benign (score 0.2855) — an in-silico prediction, not a clinical call.

CST11 p.Ile67Phe

c.199A>T · rs201830326 · VCV2509839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2855 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2855	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -10.90	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP 0.11, phastCons 0.12
Regional constraint	o/e 1.13	unconstrained · MANE · 2,302 bp · p 0.096 · regional, not allelic
Overall
CADD	18.17	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 0.0174% African / African-American · 13/74,896 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00143% 23/1,613,384 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,761
East Asian	0.0134%	7,482
Remaining individualsnot grpmax-eligible	0.0032%	31,233
Admixed American	0.00167%	60,008
South Asian	0.0011%	91,066

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.Ile67Phe
Coding: c.199A>T
MANE Select: NM_130794
dbSNP: rs201830326
Type: single nucleotide variant
Location: chr20:23452613 (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-ile67phe (accessed [today's date]).

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