Is CLPX p.Ser19Phe (c.56C>T) pathogenic?

CLPX p.Ser19Phe (c.56C>T) is classified Likely benign in CLPX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-23). AlphaMissense: likely benign (0.1781); Rare (popmax 0.297%, afr).

How common is CLPX p.Ser19Phe (c.56C>T) in the general population?

CLPX p.Ser19Phe (c.56C>T) is rare (popmax 0.297%, afr) (gnomAD).

What do computational predictors say about CLPX p.Ser19Phe (c.56C>T)?

AlphaMissense predicts likely benign (score 0.1781) — an in-silico prediction, not a clinical call.

CLPX p.Ser19Phe

c.56C>T · rs150826031 · VCV1561598

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1781 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.297%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1781	likely benign
REVEL	0.016	strongly 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 5.1	GERP 2.2, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 6,149 bp · p 4.1e-05 · regional, not allelic
Overall
CADD	18.47	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 0.297% African / African-American · 222/74,794 alleles

Filtering AF 0.265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.252%

Overall 0.0163% 258/1,584,694 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.297%	337
Admixed American	0.0221%	4,524
Remaining individualsnot grpmax-eligible	0.0179%	5,589
European (non-Finnish)	0.00111%	89,731

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.Ser19Phe
Coding: c.56C>T
MANE Select: NM_006660
dbSNP: rs150826031
Type: single nucleotide variant
Location: chr15:65185098 (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.Ser19Ala 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
CLPX p.Glu539Lys 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-ser19phe (accessed [today's date]).

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