Is CTXN2 p.Ala32Asp (c.95C>A) pathogenic?

CTXN2 p.Ala32Asp (c.95C>A) is classified Uncertain significance in CTXN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely pathogenic (0.9854); Absent from gnomAD v4.1.

How common is CTXN2 p.Ala32Asp (c.95C>A) in the general population?

CTXN2 p.Ala32Asp (c.95C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTXN2 p.Ala32Asp (c.95C>A)?

AlphaMissense predicts likely pathogenic (score 0.9854) — an in-silico prediction, not a clinical call.

CTXN2 p.Ala32Asp

c.95C>A · rs1011976238 · VCV2236880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9854 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9854	likely pathogenic · top 1% in CTXN2
REVEL	0.464	indeterminate
SaProt	LLR -12.81	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 3.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 242 bp · p 0.54 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CTXN2
Protein: p.Ala32Asp
Coding: c.95C>A
MANE Select: NM_001145668
dbSNP: rs1011976238
Type: single nucleotide variant
Location: chr15:48201395 (GRCh38)
Gene constraint: LOEUF 1.288 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 70.79

Full CTXN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTXN2 p.Ala11Thr Uncertain significance ★ ⚠ same type
CTXN2 p.Ala81Thr Uncertain significance ★ ⚠ same type
CTXN2 p.Glu77Lys Uncertain significance ★ ⚠ same type
CTXN2 p.Ile39Val Uncertain significance ★ ⚠ same type
CTXN2 p.Leu80Val 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/ctxn2-p-ala32asp (accessed [today's date]).

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