Is CEMIP2 p.Ser1320Asn (c.3959G>A) pathogenic?

CEMIP2 p.Ser1320Asn (c.3959G>A) is classified Uncertain significance in CEMIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.1544); Very rare (popmax 0.0055%, nfe).

How common is CEMIP2 p.Ser1320Asn (c.3959G>A) in the general population?

CEMIP2 p.Ser1320Asn (c.3959G>A) is very rare (popmax 0.0055%, nfe) (gnomAD).

What do computational predictors say about CEMIP2 p.Ser1320Asn (c.3959G>A)?

AlphaMissense predicts likely benign (score 0.1544) — an in-silico prediction, not a clinical call.

CEMIP2 p.Ser1320Asn

c.3959G>A · VCV4000310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0055%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1544	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.12	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 1.8	GERP 0.81, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 65 kb · p 0.015 · regional, not allelic
Overall
CADD	20.5	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 0.0055% European (non-Finnish) · 57/1,036,910 alleles

Filtering AF 0.0043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00392%

Overall 0.00466% 58/1,244,224 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0055%	18,191
Remaining individualsnot grpmax-eligible	0.00191%	52,342

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.Ser1320Asn
Coding: c.3959G>A
MANE Select: NM_013390
Type: single nucleotide variant
Location: chr9:71685390 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.66 · 1 PDB
Residue 1320: the gg-type lectin 2 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-ser1320asn (accessed [today's date]).

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