Is CSTB p.Phe54Val (c.160T>G) pathogenic?

CSTB p.Phe54Val (c.160T>G) is classified Uncertain significance in CSTB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: ambiguous (0.5516); Very rare (popmax 0.00333%, amr); Associated with progressive myoclonus epilepsy.

What condition is associated with CSTB p.Phe54Val (c.160T>G)?

CSTB p.Phe54Val (c.160T>G) is associated with progressive myoclonus epilepsy (ClinVar).

How common is CSTB p.Phe54Val (c.160T>G) in the general population?

CSTB p.Phe54Val (c.160T>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CSTB p.Phe54Val (c.160T>G)?

AlphaMissense predicts ambiguous (score 0.5516) — an in-silico prediction, not a clinical call.

CSTB p.Phe54Val

c.160T>G · rs774291632 · VCV1347664

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5516 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
AlphaMissense	0.5516	ambiguous
REVEL	0.336	indeterminate
SaProt	LLR -14.39	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,064 bp · p 0.83 · regional, not allelic
Overall
CADD	23.3	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 0.00333% Admixed American · 2/60,024 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,128 alleles · very rare

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: CSTB
Protein: p.Phe54Val
Coding: c.160T>G
MANE Select: NM_000100
dbSNP: rs774291632
Type: single nucleotide variant
Location: chr21:43774666 (GRCh38)
Gene constraint: LOEUF 1.681 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.81 · 3 PDB
Residue 54: a β-strand

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

Disease context

progressive myoclonus epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSTB c.67-1G>C Pathogenic ★★ same condition
CSTB p.Arg68Ter Pathogenic ★★ same condition
CSTB p.Gln22Ter Pathogenic/Likely pathogenic ★★ same condition
CSTB p.Gln46Ter Pathogenic/Likely pathogenic ★★ same condition
CSTB p.Ala49Thr Uncertain significance ★★ ⚠ same condition
CSTB p.Ala90Thr Uncertain significance ★★ ⚠ same condition
CSTB p.Asn52Ile Uncertain significance ★★ ⚠ same condition
CSTB p.Gln10Glu Uncertain significance ★★ ⚠ same condition

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/cstb-p-phe54val (accessed [today's date]).

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