Is CLTA p.Arg129Trp (c.385C>T) pathogenic?

CLTA p.Arg129Trp (c.385C>T) is classified Uncertain significance in CLTA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-05). AlphaMissense: ambiguous (0.4723); Ultra-rare (popmax 0.0165%, mid).

How common is CLTA p.Arg129Trp (c.385C>T) in the general population?

CLTA p.Arg129Trp (c.385C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CLTA p.Arg129Trp (c.385C>T)?

AlphaMissense predicts ambiguous (score 0.4723) — an in-silico prediction, not a clinical call.

CLTA p.Arg129Trp

c.385C>T · rs759587991 · VCV2569187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.4723	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -12.71	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.71, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 21 kb · p 0.34 · 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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00109% 16/1,461,738 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.00439%	22,762
Remaining individualsnot grpmax-eligible	0.0016%	62,500
African / African-American	0.00133%	75,018
European (non-Finnish)	0.000763%	131,104

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: CLTA
Protein: p.Arg129Trp
Coding: c.385C>T
MANE Select: NM_001833
dbSNP: rs759587991
Type: single nucleotide variant
Location: chr9:36204079 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.20 · 1 PDB
Residue 129: the 'involved in binding clathrin heavy chain' region

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

Similar variants

CLTA p.Arg129Gln Uncertain significance ★ ⚠ same residue
CLTA p.Arg129= Benign ★ same residue
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

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-arg129trp (accessed [today's date]).

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