Is CEMIP p.Arg776Trp (c.2326C>T) pathogenic?

CEMIP p.Arg776Trp (c.2326C>T) is classified Uncertain significance in CEMIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-18). AlphaMissense: likely pathogenic (0.8495); Very rare (popmax 0.00801%, afr).

How common is CEMIP p.Arg776Trp (c.2326C>T) in the general population?

CEMIP p.Arg776Trp (c.2326C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CEMIP p.Arg776Trp (c.2326C>T)?

AlphaMissense predicts likely pathogenic (score 0.8495) — an in-silico prediction, not a clinical call.

CEMIP p.Arg776Trp

c.2326C>T · VCV4225466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8495 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8495	likely pathogenic
REVEL	0.416	indeterminate
SaProt	LLR -11.26	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 3	GERP -2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 6e-09 · regional, not allelic
Overall
CADD	24.9	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

Grpmax group 0.00801% African / African-American · 6/74,894 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.0013% 21/1,613,472 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,482
East Asian	0.00223%	44,888
Admixed American	0.00167%	59,998
European (non-Finnish)	0.0011%	90,769

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.Arg776Trp
Coding: c.2326C>T
MANE Select: NM_001293298
Type: single nucleotide variant
Location: chr15:80925661 (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-arg776trp (accessed [today's date]).

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