Is CLPX p.Arg477Trp (c.1429C>T) pathogenic?

CLPX p.Arg477Trp (c.1429C>T) is classified Uncertain significance in CLPX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-09). AlphaMissense: likely benign (0.1523); Ultra-rare (popmax 0.0147%, afr).

How common is CLPX p.Arg477Trp (c.1429C>T) in the general population?

CLPX p.Arg477Trp (c.1429C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about CLPX p.Arg477Trp (c.1429C>T)?

AlphaMissense predicts likely benign (score 0.1523) — an in-silico prediction, not a clinical call.

CLPX p.Arg477Trp

c.1429C>T · rs771233943 · VCV2892609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1523 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1523	likely benign
REVEL	0.281	benign-leaning
SaProt	LLR -9.77	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 5	GERP -0.23, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 28 kb · p 8.5e-14 · 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 0.0147% African / African-American · 11/74,872 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00211% 34/1,613,914 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,807
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.005%	19,994
South Asian	0.0022%	45,534
European (non-Finnish)	0.0011%	90,770

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: CLPX
Protein: p.Arg477Trp
Coding: c.1429C>T
MANE Select: NM_006660
dbSNP: rs771233943
Type: single nucleotide variant
Location: chr15:65154964 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 67.22 · 3 PDB

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

Similar variants

CLPX p.Arg477Gln Uncertain significance ★ ⚠ same residue
CLPX p.Arg477Leu Uncertain significance ★ ⚠ same residue
CLPX p.Ala13Val Uncertain significance ★★ ⚠ same type
CLPX p.Ala65Ser Uncertain significance ★★ ⚠ same type
CLPX p.Arg270Gln Uncertain significance ★★ ⚠ same type
CLPX p.Asn424Ser Uncertain significance ★★ ⚠ same type
CLPX p.Gln352His Uncertain significance ★★ ⚠ same type
CLPX p.Gln47Arg 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/clpx-p-arg477trp (accessed [today's date]).

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