Is CSTB p.Ala14Ser (c.40G>T) pathogenic?

CSTB p.Ala14Ser (c.40G>T) is classified Uncertain significance in CSTB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-04). AlphaMissense: likely benign (0.0946); No allele count reported in gnomAD v4.1 (AN 1,531,526).

How common is CSTB p.Ala14Ser (c.40G>T) in the general population?

CSTB p.Ala14Ser (c.40G>T) is no allele count reported in gnomAD v4.1 (AN 1,531,526) (gnomAD).

What do computational predictors say about CSTB p.Ala14Ser (c.40G>T)?

AlphaMissense predicts likely benign (score 0.0946) — an in-silico prediction, not a clinical call.

CSTB p.Ala14Ser

c.40G>T · rs1169287716 · VCV2428833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0946 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,531,526)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0946	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -7.10	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 0.94	GERP -0.15, phastCons 0.025
Regional constraint	o/e 0.98	unconstrained · MANE · 2,064 bp · p 0.83 · regional, not allelic
Overall
CADD	15.82	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

No allele count reported in gnomAD v4.1 (AN 1,531,526). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CSTB
Protein: p.Ala14Ser
Coding: c.40G>T
MANE Select: NM_000100
dbSNP: rs1169287716
Type: single nucleotide variant
Location: chr21:43776230 (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 14: an α-helix

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

Similar variants

CSTB p.Ala14= Likely benign ★ same residue
CSTB c.67-1G>C Pathogenic ★★ same type
CSTB p.Arg68Ter Pathogenic ★★ same type
CSTB p.Gln22Ter Pathogenic/Likely pathogenic ★★ same type
CSTB p.Gln46Ter Pathogenic/Likely pathogenic ★★ same type
CSTB p.Ala49Thr Uncertain significance ★★ same type
CSTB p.Ala90Thr Uncertain significance ★★ ⚠ same type
CSTB p.Asn52Ile 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/cstb-p-ala14ser (accessed [today's date]).

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