Is GREM1 p.Pro50= (c.150C>T) pathogenic?

GREM1 p.Pro50= (c.150C>T) is classified Likely benign in GREM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with GREM1 p.Pro50= (c.150C>T)?

GREM1 p.Pro50= (c.150C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is GREM1 p.Pro50= (c.150C>T) in the general population?

GREM1 p.Pro50= (c.150C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

GREM1 p.Pro50=

c.150C>T · VCV3282656

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -3.1
Overall
CADD	5.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,866 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,613,804 alleles · very rare exomes 7/1,461,518 · genomes 0/152,286 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,866
European (non-Finnish)	0.000509%	196,647

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: GREM1
Protein: p.Pro50=
Coding: c.150C>T
MANE Select: NM_013372
Type: single nucleotide variant
Location: chr15:32730840 (GRCh38)
Gene constraint: LOEUF 0.856 · pLI 0.23 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 74.57 · 2 PDB
Residue 50: the 'disordered' region

Full GREM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GREM1 p.Pro50Leu Uncertain significance ★ ⚠ same residue
GREM1 p.Pro50Ser Uncertain significance ★ ⚠ same residue
GREM1 p.Arg64Trp Uncertain significance ★★ ⚠ same condition
GREM1 p.Ile103Val Uncertain significance ★★ ⚠ same condition
GREM1 p.Lys26Arg Uncertain significance ★★ ⚠ same condition
GREM1 p.Ser49Trp Uncertain significance ★★ ⚠ same condition
GREM1 p.Thr155Ala Uncertain significance ★★ ⚠ same condition
GREM1 p.Thr47Ile Uncertain significance ★★ ⚠ same condition

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/grem1-p-pro50 (accessed [today's date]).

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