Is CTDSP2 p.Glu228Lys (c.682G>A) pathogenic?

CTDSP2 p.Glu228Lys (c.682G>A) is classified Uncertain significance in CTDSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.3266); Very rare (popmax 0.00333%, amr).

How common is CTDSP2 p.Glu228Lys (c.682G>A) in the general population?

CTDSP2 p.Glu228Lys (c.682G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CTDSP2 p.Glu228Lys (c.682G>A)?

AlphaMissense predicts likely benign (score 0.3266) — an in-silico prediction, not a clinical call.

CTDSP2 p.Glu228Lys

c.682G>A · VCV4235566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3266	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -9.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 3,491 bp · p 4e-08 · regional, not allelic
Overall
CADD	26.1	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 · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000806% 13/1,613,870 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
African / African-American	0.00267%	37,447
South Asian	0.0011%	91,072
European (non-Finnish)	0.000678%	147,503

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: CTDSP2
Protein: p.Glu228Lys
Coding: c.682G>A
MANE Select: NM_005730
Type: single nucleotide variant
Location: chr12:57823912 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 78.73 · 1 PDB
Residue 228: the fcp1 homology domain; an α-helix

Full CTDSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTDSP2 p.Ala66Glu Uncertain significance ★ ⚠ same type
CTDSP2 p.Arg179Trp Uncertain significance ★ ⚠ same type
CTDSP2 p.Arg184Gln Uncertain significance ★ ⚠ same type
CTDSP2 p.Arg46Cys Uncertain significance ★ ⚠ same type
CTDSP2 p.Arg46Gly Uncertain significance ★ ⚠ same type
CTDSP2 p.Glu155Asp Uncertain significance ★ ⚠ same type
CTDSP2 p.Gly34Val Uncertain significance ★ ⚠ same type
CTDSP2 p.Ile251Thr 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/ctdsp2-p-glu228lys (accessed [today's date]).

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