Is CEMIP p.Arg206Trp (c.616C>T) pathogenic?

CEMIP p.Arg206Trp (c.616C>T) is classified Uncertain significance in CEMIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: ambiguous (0.4552); Ultra-rare (popmax 0.0134%, eas).

How common is CEMIP p.Arg206Trp (c.616C>T) in the general population?

CEMIP p.Arg206Trp (c.616C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CEMIP p.Arg206Trp (c.616C>T)?

AlphaMissense predicts ambiguous (score 0.4552) — an in-silico prediction, not a clinical call.

CEMIP p.Arg206Trp

c.616C>T · rs368428285 · VCV3142150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4552 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Computational evidence

Protein change
AlphaMissense	0.4552	ambiguous
REVEL	0.432	indeterminate
SaProt	LLR -7.32	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.003	GERP -1.7, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.085 · regional, not allelic
Overall
CADD	19.41	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 0.0134% East Asian · 6/44,882 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00211% 34/1,612,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
African / African-American	0.00267%	37,444
South Asian	0.0022%	45,526
European (non-Finnish)	0.00195%	51,261
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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.Arg206Trp
Coding: c.616C>T
MANE Select: NM_001293298
dbSNP: rs368428285
Type: single nucleotide variant
Location: chr15:80881135 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69
Residue 206: the gg-type lectin 1 domain

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

Similar variants

CEMIP p.Arg206Gln Uncertain significance ★ ⚠ same residue
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

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-arg206trp (accessed [today's date]).

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