Is CEMIP2 p.Arg409Leu (c.1226G>T) pathogenic?

CEMIP2 p.Arg409Leu (c.1226G>T) is classified Uncertain significance in CEMIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.1122); Absent from gnomAD v4.1.

How common is CEMIP2 p.Arg409Leu (c.1226G>T) in the general population?

CEMIP2 p.Arg409Leu (c.1226G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEMIP2 p.Arg409Leu (c.1226G>T)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

CEMIP2 p.Arg409Leu

c.1226G>T · VCV4000333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,798)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -5.72	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 0.24	GERP -0.78, phastCons 0.011
Regional constraint	o/e 0.94	unconstrained · MANE · 65 kb · p 0.015 · regional, not allelic
Overall
CADD	21.4	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

No allele count reported in gnomAD v4.1 (AN 1,608,798). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CEMIP2
Protein: p.Arg409Leu
Coding: c.1226G>T
MANE Select: NM_013390
Type: single nucleotide variant
Location: chr9:71734973 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.66 · 1 PDB
Residue 409: the gg-type lectin 1 domain; a β-strand

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

Similar variants

CEMIP2 p.Arg409Gln Uncertain significance ★ ⚠ same residue
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

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-arg409leu (accessed [today's date]).

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