Is CEMIP2 p.Val796Ile (c.2386G>A) pathogenic?

CEMIP2 p.Val796Ile (c.2386G>A) is classified Uncertain significance in CEMIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.0584); Ultra-rare (popmax 0.0135%, sas).

How common is CEMIP2 p.Val796Ile (c.2386G>A) in the general population?

CEMIP2 p.Val796Ile (c.2386G>A) is ultra-rare (popmax 0.0135%, sas) (gnomAD).

What do computational predictors say about CEMIP2 p.Val796Ile (c.2386G>A)?

AlphaMissense predicts likely benign (score 0.0584) — an in-silico prediction, not a clinical call.

CEMIP2 p.Val796Ile

c.2386G>A · VCV4000317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0584 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0584	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -5.61	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 2.2	GERP -0.13, phastCons 0.98
Regional constraint	o/e 0.94	unconstrained · MANE · 65 kb · p 0.015 · regional, not allelic
Overall
CADD	17.52	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0135% South Asian · 12/88,694 alleles

Filtering AF 0.00779% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00608%

Overall 0.00193% 31/1,604,736 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0135%	7,391
African / African-American	0.00401%	24,909
Remaining individualsnot grpmax-eligible	0.00161%	62,032
European (non-Finnish)	0.00128%	78,397

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.Val796Ile
Coding: c.2386G>A
MANE Select: NM_013390
Type: single nucleotide variant
Location: chr9:71717961 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.66 · 1 PDB
Residue 796: a β-strand

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-val796ile (accessed [today's date]).

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