Is CTDSPL p.Arg262Gln (c.785G>A) pathogenic?

CTDSPL p.Arg262Gln (c.785G>A) is classified Uncertain significance in CTDSPL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.0561); Very rare (popmax 0.00267%, afr).

How common is CTDSPL p.Arg262Gln (c.785G>A) in the general population?

CTDSPL p.Arg262Gln (c.785G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CTDSPL p.Arg262Gln (c.785G>A)?

AlphaMissense predicts likely benign (score 0.0561) — an in-silico prediction, not a clinical call.

CTDSPL p.Arg262Gln

c.785G>A · rs756522638 · VCV2515566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0561 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0561	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -7.08	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 2.5	GERP -0.44, phastCons 0.99
Regional constraint	o/e 0.60	unconstrained · MANE · 5,154 bp · p 2.7e-06 · regional, not allelic
Overall
CADD	21.6	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 0.00267% African / African-American · 2/74,926 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00136% 22/1,614,034 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,463
East Asian	0.00223%	44,880
Admixed American	0.00167%	60,006
European (non-Finnish)	0.00144%	69,413
South Asian	0.0011%	91,078

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.Arg262Gln
Coding: c.785G>A
MANE Select: NM_001008392
dbSNP: rs756522638
Type: single nucleotide variant
Location: chr3:37980821 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.64 · 1 PDB

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

Similar variants

CTDSPL p.Arg262Trp Uncertain significance ★ ⚠ same residue
CTDSPL p.Ala92Thr Uncertain significance ★ ⚠ same type
CTDSPL p.Arg184His Uncertain significance ★ ⚠ same type
CTDSPL p.Arg210Cys 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
CTDSPL p.Gln29His 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-arg262gln (accessed [today's date]).

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