Is CTAG2 p.Ala71Val (c.212C>T) pathogenic?

CTAG2 p.Ala71Val (c.212C>T) is classified Uncertain significance in CTAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely benign (0.1396); Very rare (popmax 0.00657%, amr).

How common is CTAG2 p.Ala71Val (c.212C>T) in the general population?

CTAG2 p.Ala71Val (c.212C>T) is very rare (popmax 0.00657%, amr) (gnomAD).

What do computational predictors say about CTAG2 p.Ala71Val (c.212C>T)?

AlphaMissense predicts likely benign (score 0.1396) — an in-silico prediction, not a clinical call.

CTAG2 p.Ala71Val

c.212C>T · VCV4007799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1396 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00657%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1396	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -7.76	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 -1.3	GERP -1.6, phastCons 0.001
Regional constraint	o/e 0.97	unconstrained · MANE · 1,329 bp · p 0.74 · regional, not allelic
Overall
CADD	1.88	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 0.00657% Admixed American · 3/45,685 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000883%

Overall 0.000912% 11/1,205,745 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00657%	15,228
Finnishnot grpmax-eligible	0.00439%	22,787
South Asian	0.00354%	28,243
Remaining individualsnot grpmax-eligible	0.00211%	47,485
European (non-Finnish)	0.000336%	297,843

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: CTAG2
Protein: p.Ala71Val
Coding: c.212C>T
MANE Select: NM_172377
Type: single nucleotide variant
Location: chrX:154653304 (GRCh38)
Structure: AlphaFold pLDDT 47.90
Residue 71: the 'disordered' region

Full CTAG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTAG2 c.405-28T>C Likely benign ★★ same type
CTAG2 c.405-93G>C Benign ★★ same type
CTAG2 p.Met94Val Benign ★★ same type
CTAG2 p.Pro99Ala Benign ★★ same type
CTAG2 c.404+107C>A Uncertain significance ★ ⚠ same type
CTAG2 c.404+21G>C Uncertain significance ★ ⚠ same type
CTAG2 c.404+35C>T Uncertain significance ★ ⚠ same type
CTAG2 c.404+42G>A 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/ctag2-p-ala71val (accessed [today's date]).

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