Is CEMP1 p.Pro35Arg (c.104C>G) pathogenic?

CEMP1 p.Pro35Arg (c.104C>G) is classified Uncertain significance in CEMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-06). AlphaMissense: likely benign (0.1407); Very rare (popmax 0.00017%, nfe).

How common is CEMP1 p.Pro35Arg (c.104C>G) in the general population?

CEMP1 p.Pro35Arg (c.104C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CEMP1 p.Pro35Arg (c.104C>G)?

AlphaMissense predicts likely benign (score 0.1407) — an in-silico prediction, not a clinical call.

CEMP1 p.Pro35Arg

c.104C>G · rs2066086704 · VCV2317258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1407 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1407	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -6.78	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 0.38, phastCons 0.002
Regional constraint	o/e 1.22	unconstrained · MANE · 740 bp · p 8.3e-05 · regional, not allelic
Overall
CADD	10.31	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 0.00017% European (non-Finnish) · 2/1,179,914 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,506 alleles · very rare exomes 2/1,461,210 · genomes 0/152,296 · joint denominator

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: CEMP1
Protein: p.Pro35Arg
Coding: c.104C>G
MANE Select: NM_001048212
dbSNP: rs2066086704
Type: single nucleotide variant
Location: chr16:2530970 (GRCh38)
Structure: AlphaFold pLDDT 35.92 · 1 PDB
Residue 35: the 'disordered' region

Full CEMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEMP1 p.Ala153Val Uncertain significance ★ ⚠ same type
CEMP1 p.Ala49Thr Uncertain significance ★ ⚠ same type
CEMP1 p.Ala62Val Uncertain significance ★ ⚠ same type
CEMP1 p.Arg155Ser Uncertain significance ★ ⚠ same type
CEMP1 p.Arg161Ser Uncertain significance ★ ⚠ same type
CEMP1 p.Arg80Cys Uncertain significance ★ ⚠ same type
CEMP1 p.Arg80Ser Uncertain significance ★ ⚠ same type
CEMP1 p.Arg94Lys 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/cemp1-p-pro35arg (accessed [today's date]).

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