Is MUC1 p.Pro253Ser (c.757C>T) pathogenic?

MUC1 p.Pro253Ser (c.757C>T) is classified Uncertain significance in MUC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MUC1 p.Pro253Ser (c.757C>T)?

MUC1 p.Pro253Ser (c.757C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MUC1 p.Pro253Ser (c.757C>T) in the general population?

MUC1 p.Pro253Ser (c.757C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

MUC1 p.Pro253Ser

c.757C>T · VCV4112203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.36	GERP -1.8
Overall
CADD	0.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,968 alleles

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

Overall 0.000124% 2/1,612,724 alleles · very rare exomes 1/1,460,538 · genomes 1/152,186 · 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: MUC1
Protein: p.Pro253Ser
Coding: c.757C>T
Type: single nucleotide variant
Location: chr1:155188321 (GRCh38)
Gene constraint: LOEUF 0.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.92 · 23 PDB
Residue 253: the 'disordered' region; the '42 x 20 aa approximate tandem repeats of p-a-p-g-s-t-a-p-p-a-h-g-v-t-s-a-p-d-t-r' region

Full MUC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MUC1 p.Ala116Pro Uncertain significance ★ same condition
MUC1 p.Ala124Thr Uncertain significance ★ same condition
MUC1 p.Ala130Asp Uncertain significance ★ same condition
MUC1 p.Ala136Asp Uncertain significance ★ same condition
MUC1 p.Ala141Val Uncertain significance ★ same condition
MUC1 p.Ala161Val Uncertain significance ★ same condition
MUC1 p.Ala170Asp Uncertain significance ★ same condition
MUC1 p.Ala176Ser 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/muc1-p-pro253ser (accessed [today's date]).

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