Is CTDSPL2 p.Ile78Val (c.232A>G) pathogenic?

CTDSPL2 p.Ile78Val (c.232A>G) is classified Uncertain significance in CTDSPL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: likely benign (0.0587); Very rare (popmax 0.00458%, nfe).

How common is CTDSPL2 p.Ile78Val (c.232A>G) in the general population?

CTDSPL2 p.Ile78Val (c.232A>G) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about CTDSPL2 p.Ile78Val (c.232A>G)?

AlphaMissense predicts likely benign (score 0.0587) — an in-silico prediction, not a clinical call.

CTDSPL2 p.Ile78Val

c.232A>G · VCV3498153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0587 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0587	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -5.66	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 6.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.6 · regional, not allelic
Overall
CADD	16.35	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 0.00458% European (non-Finnish) · 54/1,178,040 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00322%

Overall 0.0036% 58/1,611,720 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,816
African / African-American	0.00401%	24,945
Admixed American	0.00167%	59,980

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.Ile78Val
Coding: c.232A>G
MANE Select: NM_016396
Type: single nucleotide variant
Location: chr15:44484269 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.94
Residue 78: the 'disordered' region

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

Similar variants

CTDSPL2 p.Ala244Val Benign ★★ same type
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

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-ile78val (accessed [today's date]).

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