Is CEMIP p.Arg754Gln (c.2261G>A) pathogenic?

CEMIP p.Arg754Gln (c.2261G>A) is classified Uncertain significance in CEMIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: ambiguous (0.445); Ultra-rare (popmax 0.099%, mid).

How common is CEMIP p.Arg754Gln (c.2261G>A) in the general population?

CEMIP p.Arg754Gln (c.2261G>A) is ultra-rare (popmax 0.099%, mid) (gnomAD).

What do computational predictors say about CEMIP p.Arg754Gln (c.2261G>A)?

AlphaMissense predicts ambiguous (score 0.445) — an in-silico prediction, not a clinical call.

CEMIP p.Arg754Gln

c.2261G>A · rs202038667 · VCV3142137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.445 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Computational evidence

Protein change
AlphaMissense	0.445	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -7.65	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 6e-09 · regional, not allelic
Overall
CADD	29.5	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 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.00855% 138/1,614,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
European (non-Finnish)	0.00983%	10,173
African / African-American	0.00933%	10,719
Remaining individualsnot grpmax-eligible	0.008%	12,501
Admixed American	0.00333%	30,014
South Asian	0.0022%	45,536

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: CEMIP
Protein: p.Arg754Gln
Coding: c.2261G>A
MANE Select: NM_001293298
dbSNP: rs202038667
Type: single nucleotide variant
Location: chr15:80924679 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69

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

Similar variants

CEMIP p.Ala33Val Uncertain significance ★★ ⚠ same type
CEMIP p.Gly870Asp Uncertain significance ★★ ⚠ same type
CEMIP c.1086+82T>A Benign ★★ same type
CEMIP c.1087-239G>A Benign ★★ same type
CEMIP c.1412-76G>A Benign ★★ same type
CEMIP c.1587+57A>G Benign ★★ same type
CEMIP c.1587+79G>A Benign ★★ same type
CEMIP c.1797+102T>C Benign ★★ 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/cemip-p-arg754gln (accessed [today's date]).

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