Is CLPX p.Asp583His (c.1747G>C) pathogenic?

CLPX p.Asp583His (c.1747G>C) is classified Uncertain significance in CLPX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). AlphaMissense: likely pathogenic (0.7035); Absent from gnomAD v4.1.

How common is CLPX p.Asp583His (c.1747G>C) in the general population?

CLPX p.Asp583His (c.1747G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLPX p.Asp583His (c.1747G>C)?

AlphaMissense predicts likely pathogenic (score 0.7035) — an in-silico prediction, not a clinical call.

CLPX p.Asp583His

c.1747G>C · rs2087734900 · VCV3145991

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7035 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7035	likely pathogenic
REVEL	0.408	indeterminate
SaProt	LLR -12.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 28 kb · p 8.5e-14 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CLPX
Protein: p.Asp583His
Coding: c.1747G>C
MANE Select: NM_006660
dbSNP: rs2087734900
Type: single nucleotide variant
Location: chr15:65152494 (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.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
CLPX p.Glu539Lys Uncertain significance ★★ ⚠ same type
CLPX p.Glu614Gly 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-asp583his (accessed [today's date]).

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