Is POMP p.Leu30Phe (c.88C>T) pathogenic?

POMP p.Leu30Phe (c.88C>T) is classified Uncertain significance in POMP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-23). AlphaMissense: likely benign (0.1083); Ultra-rare (popmax 0.0133%, afr); Associated with Inborn genetic diseases.

What condition is associated with POMP p.Leu30Phe (c.88C>T)?

POMP p.Leu30Phe (c.88C>T) is associated with Inborn genetic diseases (ClinVar).

How common is POMP p.Leu30Phe (c.88C>T) in the general population?

POMP p.Leu30Phe (c.88C>T) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about POMP p.Leu30Phe (c.88C>T)?

AlphaMissense predicts likely benign (score 0.1083) — an in-silico prediction, not a clinical call.

POMP p.Leu30Phe

c.88C>T · rs371032321 · VCV1509396

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1083 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1083	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -7.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 19 kb · p 0.048 · regional, not allelic
Overall
CADD	22.7	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 0.0133% African / African-American · 10/74,934 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000621% 10/1,611,250 alleles · ultra-rare exomes 2/1,459,016 · genomes 8/152,234 · 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.Leu30Phe
Coding: c.88C>T
MANE Select: NM_015932
dbSNP: rs371032321
Type: single nucleotide variant
Location: chr13:28662494 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 81.76 · 11 PDB
Residue 30: a turn

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.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.Leu6Pro Uncertain significance ★★ ⚠ same condition
POMP p.Pro76Ser Uncertain significance ★★ ⚠ same condition
POMP p.Ser65Phe 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-leu30phe (accessed [today's date]).

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