Is POMP p.Arg91Cys (c.271C>T) pathogenic?

POMP p.Arg91Cys (c.271C>T) is classified Uncertain significance in POMP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-26). AlphaMissense: ambiguous (0.3602); Very rare (popmax 0.000171%, nfe); Associated with Inborn genetic diseases.

What condition is associated with POMP p.Arg91Cys (c.271C>T)?

POMP p.Arg91Cys (c.271C>T) is associated with Inborn genetic diseases (ClinVar).

How common is POMP p.Arg91Cys (c.271C>T) in the general population?

POMP p.Arg91Cys (c.271C>T) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about POMP p.Arg91Cys (c.271C>T)?

AlphaMissense predicts ambiguous (score 0.3602) — an in-silico prediction, not a clinical call.

POMP p.Arg91Cys

c.271C>T · VCV4840550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3602	ambiguous
REVEL	0.596	indeterminate
SaProt	LLR -13.84	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 19 kb · p 0.048 · regional, not allelic
Overall
CADD	26.3	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 0.000171% European (non-Finnish) · 2/1,172,332 alleles

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

Overall 0.000125% 2/1,605,524 alleles · very rare exomes 2/1,453,266 · genomes 0/152,258 · 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: POMP
Protein: p.Arg91Cys
Coding: c.271C>T
MANE Select: NM_015932
Type: single nucleotide variant
Location: chr13:28672345 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 81.76 · 11 PDB

Full POMP 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

POMP p.Arg91His Uncertain significance ★ ⚠ same residue
POMP p.Asn108His Uncertain significance ★★ ⚠ same condition
POMP p.Asn40Ser Uncertain significance ★★ ⚠ same condition
POMP p.Gln56His Uncertain significance ★★ ⚠ same condition
POMP p.His28Pro Uncertain significance ★★ ⚠ same condition
POMP p.Ile112Val Uncertain significance ★★ ⚠ same condition
POMP p.Leu30Phe Uncertain significance ★★ ⚠ same condition
POMP p.Leu6Pro 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/pomp-p-arg91cys (accessed [today's date]).

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