Is CLTA p.Ala214Pro (c.640G>C) pathogenic?

CLTA p.Ala214Pro (c.640G>C) is classified Uncertain significance in CLTA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely pathogenic (0.9263); Absent from gnomAD v4.1.

How common is CLTA p.Ala214Pro (c.640G>C) in the general population?

CLTA p.Ala214Pro (c.640G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLTA p.Ala214Pro (c.640G>C)?

AlphaMissense predicts likely pathogenic (score 0.9263) — an in-silico prediction, not a clinical call.

CLTA p.Ala214Pro

c.640G>C · VCV3834205

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9263 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9263	likely pathogenic
REVEL	0.233	benign-leaning
SaProt	LLR -14.35	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.56, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 21 kb · p 0.34 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A244P vs ClinVar A214P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLTA
Protein: p.Ala214Pro
Coding: c.640G>C
MANE Select: NM_001833
Type: single nucleotide variant
Location: chr9:36211757 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.20 · 1 PDB

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

Similar variants

CLTA c.256-6G>A Benign ★★ same type
CLTA c.486-2284G>A Uncertain significance ★ ⚠ same type
CLTA c.486-971A>G Uncertain significance ★ ⚠ same type
CLTA p.Ala11Gly Uncertain significance ★ ⚠ same type
CLTA p.Ala133Thr Uncertain significance ★ same type
CLTA p.Ala18Thr Uncertain significance ★ ⚠ same type
CLTA p.Ala51Thr Uncertain significance ★ ⚠ same type
CLTA p.Ala51Val 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/clta-p-ala214pro (accessed [today's date]).

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