Is CLASRP p.Arg643Gln (c.1928G>A) pathogenic?

CLASRP p.Arg643Gln (c.1928G>A) is classified Uncertain significance in CLASRP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: ambiguous (0.4779); Ultra-rare (popmax 0.0245%, eas).

How common is CLASRP p.Arg643Gln (c.1928G>A) in the general population?

CLASRP p.Arg643Gln (c.1928G>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about CLASRP p.Arg643Gln (c.1928G>A)?

AlphaMissense predicts ambiguous (score 0.4779) — an in-silico prediction, not a clinical call.

CLASRP p.Arg643Gln

c.1928G>A · rs142939842 · VCV2607597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4779 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4779	ambiguous
REVEL	0.155	moderately benign-leaning
SaProt	LLR -10.30	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 2,816 bp · p 0.00025 · regional, not allelic
Overall
CADD	29.4	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 0.0245% East Asian · 11/44,872 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00299% 48/1,607,474 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,079
Middle Eastern	0.0165%	6,070
South Asian	0.0033%	30,315
European (non-Finnish)	0.00264%	37,875
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.00161%	62,250

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: CLASRP
Protein: p.Arg643Gln
Coding: c.1928G>A
MANE Select: NM_007056
dbSNP: rs142939842
Type: single nucleotide variant
Location: chr19:45070075 (GRCh38)
Gene constraint: LOEUF 0.699 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.62
Residue 643: the 'disordered' region

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

Similar variants

CLASRP p.Ala157Thr Uncertain significance ★ ⚠ same type
CLASRP p.Ala231Val Uncertain significance ★ ⚠ same type
CLASRP p.Ala346Gly Uncertain significance ★ ⚠ same type
CLASRP p.Ala371Thr Uncertain significance ★ ⚠ same type
CLASRP p.Ala415Thr Uncertain significance ★ ⚠ same type
CLASRP p.Ala545Pro Uncertain significance ★ ⚠ same type
CLASRP p.Ala549Val Uncertain significance ★ ⚠ same type
CLASRP p.Ala561Thr 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/clasrp-p-arg643gln (accessed [today's date]).

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