Is UMOD p.Ser367Pro (c.1099T>C) pathogenic?

UMOD p.Ser367Pro (c.1099T>C) is classified Uncertain significance in UMOD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.217); Very rare (popmax 0.00534%, afr).

How common is UMOD p.Ser367Pro (c.1099T>C) in the general population?

UMOD p.Ser367Pro (c.1099T>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about UMOD p.Ser367Pro (c.1099T>C)?

AlphaMissense predicts likely benign (score 0.217) — an in-silico prediction, not a clinical call.

UMOD p.Ser367Pro

c.1099T>C · rs1010239177 · VCV1957788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.217 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.217	likely benign
REVEL	0.616	indeterminate
SaProt	LLR -8.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -0.14, phastCons 0.96
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.0029 · regional, not allelic
Overall
CADD	16.91	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 0.00534% African / African-American · 4/74,938 alleles

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

Overall 0.000248% 4/1,614,090 alleles · very rare exomes 0/1,461,884 · genomes 4/152,206 · 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: UMOD
Protein: p.Ser367Pro
Coding: c.1099T>C
MANE Select: NM_003361
dbSNP: rs1010239177
Type: single nucleotide variant
Location: chr16:20346209 (GRCh38)
Gene constraint: LOEUF 1.241 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.00 · 10 PDB
Residue 367: the 'zp-n' region; the zp domain

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

Similar variants

UMOD p.Ser367Leu Uncertain significance ★★ ⚠ same residue
UMOD p.Ser367Trp Uncertain significance ★★ ⚠ same residue
UMOD p.Ala285Glu Pathogenic ★★ same type
UMOD p.Ala461Glu Likely pathogenic ★★ same type
UMOD p.Arg185Cys Pathogenic ★★ same type
UMOD p.Arg204Gly Pathogenic/Likely pathogenic ★★ same type
UMOD p.Cys106Tyr Pathogenic/Likely pathogenic ★★ same type
UMOD p.Cys112Tyr Pathogenic/Likely pathogenic ★★ 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/umod-p-ser367pro (accessed [today's date]).

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