Is CTDSPL p.Glu153Lys (c.457G>A) pathogenic?

CTDSPL p.Glu153Lys (c.457G>A) is classified Uncertain significance in CTDSPL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely benign (0.2476); Ultra-rare (popmax 0.0356%, eas).

How common is CTDSPL p.Glu153Lys (c.457G>A) in the general population?

CTDSPL p.Glu153Lys (c.457G>A) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

What do computational predictors say about CTDSPL p.Glu153Lys (c.457G>A)?

AlphaMissense predicts likely benign (score 0.2476) — an in-silico prediction, not a clinical call.

CTDSPL p.Glu153Lys

c.457G>A · VCV3498151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2476 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2476	likely benign
REVEL	0.384	indeterminate
SaProt	LLR -11.10	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 6,873 bp · p 2.9e-05 · regional, not allelic
Overall
CADD	33.0	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 0.0356% East Asian · 16/44,904 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00316% 51/1,614,066 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,806
African / African-American	0.004%	24,983
European (non-Finnish)	0.00263%	38,066
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: CTDSPL
Protein: p.Glu153Lys
Coding: c.457G>A
MANE Select: NM_001008392
Type: single nucleotide variant
Location: chr3:37971437 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.64 · 1 PDB
Residue 153: the fcp1 homology domain; an α-helix

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

Similar variants

CTDSPL p.Ala92Thr Uncertain significance ★ ⚠ same type
CTDSPL p.Arg184His Uncertain significance ★ ⚠ same type
CTDSPL p.Arg210Cys Uncertain significance ★ ⚠ same type
CTDSPL p.Arg262Gln Uncertain significance ★ ⚠ same type
CTDSPL p.Arg262Trp Uncertain significance ★ ⚠ same type
CTDSPL p.Asn12Ser Uncertain significance ★ ⚠ same type
CTDSPL p.Asn275Lys Uncertain significance ★ ⚠ same type
CTDSPL p.Asp265Asn 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/ctdspl-p-glu153lys (accessed [today's date]).

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