Is CTNS p.Ala244Val (c.731C>T) pathogenic?

CTNS p.Ala244Val (c.731C>T) is classified Uncertain significance in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.1233); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Ala244Val (c.731C>T)?

CTNS p.Ala244Val (c.731C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTNS p.Ala244Val (c.731C>T) in the general population?

CTNS p.Ala244Val (c.731C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CTNS p.Ala244Val (c.731C>T)?

AlphaMissense predicts likely benign (score 0.1233) — an in-silico prediction, not a clinical call.

CTNS p.Ala244Val

c.731C>T · VCV4616721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1233 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1233	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -7.71	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 0.24	GERP -3.4
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.4 · regional, not allelic
Overall
CADD	17.49	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 0.00333% Admixed American · 2/60,014 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00118% 19/1,611,840 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,007
South Asian	0.0022%	45,508
Remaining individualsnot grpmax-eligible	0.0016%	62,306
African / African-American	0.00134%	74,894
European (non-Finnish)	0.0011%	90,768

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: CTNS
Protein: p.Ala244Val
Coding: c.731C>T
MANE Select: NM_004937
Type: single nucleotide variant
Location: chr17:3658054 (GRCh38)
Gene constraint: LOEUF 0.754 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB
Residue 244: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTNS p.Ala244Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CTNS p.Ala244= Likely benign ★ same residue
CTNS c.140+2T>C Pathogenic/Likely pathogenic ★★ same condition
CTNS c.61+5G>A Pathogenic/Likely pathogenic ★★ same condition
CTNS c.970+5G>A Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Ala212Val Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Asn323Lys Pathogenic ★★ same condition
CTNS p.Ser139Phe Pathogenic/Likely pathogenic ★★ 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/ctns-p-ala244val (accessed [today's date]).

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