Is MUC1 p.Ser80Phe (c.239C>T) pathogenic?

MUC1 p.Ser80Phe (c.239C>T) is classified Uncertain significance in MUC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). Very rare (popmax 0.00535%, afr); Associated with Inborn genetic diseases.

What condition is associated with MUC1 p.Ser80Phe (c.239C>T)?

MUC1 p.Ser80Phe (c.239C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MUC1 p.Ser80Phe (c.239C>T) in the general population?

MUC1 p.Ser80Phe (c.239C>T) is very rare (popmax 0.00535%, afr) (gnomAD).

MUC1 p.Ser80Phe

c.239C>T · rs754388111 · VCV2328034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.067	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -1.8
Overall
CADD	8.273	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00535% African / African-American · 4/74,814 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,030 alleles · very rare exomes 2/1,461,032 · genomes 2/151,998 · 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.Ser80Phe
Coding: c.239C>T
dbSNP: rs754388111
Type: single nucleotide variant
Location: chr1:155192130 (GRCh38)
Gene constraint: LOEUF 0.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.92 · 23 PDB
Residue 80: the 'disordered' 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-ser80phe (accessed [today's date]).

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