Is CTDSPL2 p.Ala244Val (c.731C>T) pathogenic?

CTDSPL2 p.Ala244Val (c.731C>T) is classified Benign in CTDSPL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-29). AlphaMissense: likely benign (0.1048); Low-frequency (popmax 3.79%, afr).

How common is CTDSPL2 p.Ala244Val (c.731C>T) in the general population?

CTDSPL2 p.Ala244Val (c.731C>T) is low-frequency (popmax 3.79%, afr) (gnomAD).

What do computational predictors say about CTDSPL2 p.Ala244Val (c.731C>T)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

CTDSPL2 p.Ala244Val

c.731C>T · rs871923 · VCV714596

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.79%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.24	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 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.6 · regional, not allelic
Overall
CADD	23.0	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 3.79% African / African-American · 2,842/74,994 alleles

Filtering AF 3.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.63%

Overall 0.195% 3,145/1,613,778 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.79%	26
Remaining individualsnot grpmax-eligible	0.238%	419
Admixed American	0.16%	625
Middle Eastern	0.033%	3,031
South Asian	0.0187%	5,358
European (non-Finnish)	0.00322%	31,047
Finnishnot grpmax-eligible	0.00156%	63,944

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: CTDSPL2
Protein: p.Ala244Val
Coding: c.731C>T
MANE Select: NM_016396
dbSNP: rs871923
Type: single nucleotide variant
Location: chr15:44496419 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.94
Residue 244: a UniProt-annotated variant site (in)

Full CTDSPL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTDSPL2 p.Pro166= Benign ★★ same type
CTDSPL2 p.Ala199Pro Uncertain significance ★ ⚠ same type
CTDSPL2 p.Ala204Gly Uncertain significance ★ ⚠ same type
CTDSPL2 p.Ala231Thr Uncertain significance ★ ⚠ same type
CTDSPL2 p.Ala8Gly Uncertain significance ★ ⚠ same type
CTDSPL2 p.Ala8Thr Uncertain significance ★ ⚠ same type
CTDSPL2 p.Arg19Cys Uncertain significance ★ ⚠ same type
CTDSPL2 p.Arg224Cys 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/ctdspl2-p-ala244val (accessed [today's date]).

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