Is CEMP1 p.Cys232Phe (c.695G>T) pathogenic?

CEMP1 p.Cys232Phe (c.695G>T) is classified Uncertain significance in CEMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: ambiguous (0.3746); Ultra-rare (popmax 0.0247%, nfe).

How common is CEMP1 p.Cys232Phe (c.695G>T) in the general population?

CEMP1 p.Cys232Phe (c.695G>T) is ultra-rare (popmax 0.0247%, nfe) (gnomAD).

What do computational predictors say about CEMP1 p.Cys232Phe (c.695G>T)?

AlphaMissense predicts ambiguous (score 0.3746) — an in-silico prediction, not a clinical call.

CEMP1 p.Cys232Phe

c.695G>T · rs369689531 · VCV3142220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0247%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3746	ambiguous
REVEL	0.117	moderately benign-leaning
SaProt	LLR -6.91	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -1.2, phastCons 0.005
Regional constraint	o/e 1.22	unconstrained · MANE · 740 bp · p 8.3e-05 · regional, not allelic
Overall
CADD	14.78	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 0.0247% European (non-Finnish) · 292/1,180,004 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0215%

Overall 0.0182% 294/1,613,872 alleles · ultra-rare exomes 279/1,461,652 · genomes 15/152,220 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0247%	4,041
Remaining individualsnot grpmax-eligible	0.0016%	62,468
African / African-American	0.00133%	74,944

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.Cys232Phe
Coding: c.695G>T
MANE Select: NM_001048212
dbSNP: rs369689531
Type: single nucleotide variant
Location: chr16:2530379 (GRCh38)
Structure: AlphaFold pLDDT 35.92 · 1 PDB

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-cys232phe (accessed [today's date]).

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