Is CEMIP2 p.Arg195Cys (c.583C>T) pathogenic?

CEMIP2 p.Arg195Cys (c.583C>T) is classified Uncertain significance in CEMIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely benign (0.1577); Very rare (popmax 0.00668%, afr).

How common is CEMIP2 p.Arg195Cys (c.583C>T) in the general population?

CEMIP2 p.Arg195Cys (c.583C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about CEMIP2 p.Arg195Cys (c.583C>T)?

AlphaMissense predicts likely benign (score 0.1577) — an in-silico prediction, not a clinical call.

CEMIP2 p.Arg195Cys

c.583C>T · VCV4000331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1577 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1577	likely benign
REVEL	0.7	pathogenic-leaning
SaProt	LLR -9.28	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 65 kb · p 0.015 · regional, not allelic
Overall
CADD	32.0	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 0.00668% African / African-American · 5/74,806 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.0026% 42/1,613,464 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,961
European (non-Finnish)	0.00288%	34,700
East Asian	0.00223%	44,868
Remaining individualsnot grpmax-eligible	0.0016%	62,470
South Asian	0.0011%	91,040

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: CEMIP2
Protein: p.Arg195Cys
Coding: c.583C>T
MANE Select: NM_013390
Type: single nucleotide variant
Location: chr9:71745469 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.66 · 1 PDB
Residue 195: the g8 domain

Full CEMIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEMIP2 p.Asp164Val Uncertain significance ★★ ⚠ same type
CEMIP2 p.Cys453Tyr Pathogenic ★ same type
CEMIP2 p.Trp1048Ter Pathogenic ★ same type
CEMIP2 c.2399+1G>A Uncertain significance ★ same type
CEMIP2 p.Ala1134Gly Uncertain significance ★ ⚠ same type
CEMIP2 p.Ala1168Val Uncertain significance ★ ⚠ same type
CEMIP2 p.Ala186Val Uncertain significance ★ ⚠ same type
CEMIP2 p.Ala191Gly 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/cemip2-p-arg195cys (accessed [today's date]).

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