Is CLTC p.Arg950Gln (c.2849G>A) pathogenic?

CLTC p.Arg950Gln (c.2849G>A) is classified Uncertain significance in CLTC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-21). AlphaMissense: ambiguous (0.5254); Very rare (popmax 6.86e-05%).

How common is CLTC p.Arg950Gln (c.2849G>A) in the general population?

CLTC p.Arg950Gln (c.2849G>A) is very rare (popmax 6.86e-05%) (gnomAD).

What do computational predictors say about CLTC p.Arg950Gln (c.2849G>A)?

AlphaMissense predicts ambiguous (score 0.5254) — an in-silico prediction, not a clinical call.

CLTC p.Arg950Gln

c.2849G>A · rs747671478 · VCV1955492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5254 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.86e-05%)

Computational evidence

Protein change
AlphaMissense	0.5254	ambiguous
REVEL	0.591	indeterminate
SaProt	LLR -5.40	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 13 kb · p 3.4e-42 · 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 6.86e-05%

Overall 6.86e-05% 1/1,457,214 alleles · very rare

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: CLTC
Protein: p.Arg950Gln
Coding: c.2849G>A
MANE Select: NM_004859
dbSNP: rs747671478
Type: single nucleotide variant
Location: chr17:59679449 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.62 · 10 PDB
Residue 950: the 'heavy chain arm' region; the 'proximal segment' region

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

Similar variants

CLTC p.Arg1165Ter Likely pathogenic ★★ same type
CLTC p.Arg1251Ter Pathogenic/Likely pathogenic ★★ same type
CLTC p.Arg1311Ter Likely pathogenic ★★ same type
CLTC p.Arg63Ter Pathogenic ★★ same type
CLTC p.Pro890Leu Pathogenic/Likely pathogenic ★★ same type
CLTC p.Tyr1574Ter Pathogenic/Likely pathogenic ★★ same type
CLTC p.Tyr803Ter Pathogenic/Likely pathogenic ★★ same type
CLTC c.4605+3T>A 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/cltc-p-arg950gln (accessed [today's date]).

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