Is POMP p.His28Pro (c.83A>C) pathogenic?

POMP p.His28Pro (c.83A>C) is classified Uncertain significance in POMP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-08). AlphaMissense: likely benign (0.0764); Rare (popmax 0.108%, nfe); Associated with Inborn genetic diseases.

What condition is associated with POMP p.His28Pro (c.83A>C)?

POMP p.His28Pro (c.83A>C) is associated with Inborn genetic diseases (ClinVar).

How common is POMP p.His28Pro (c.83A>C) in the general population?

POMP p.His28Pro (c.83A>C) is rare (popmax 0.108%, nfe) (gnomAD).

What do computational predictors say about POMP p.His28Pro (c.83A>C)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

POMP p.His28Pro

c.83A>C · rs140397494 · VCV1449348

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -6.66	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 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 19 kb · p 0.048 · regional, not allelic
Overall
CADD	20.8	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 0.108% European (non-Finnish) · 1,271/1,178,558 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.083% 1,338/1,612,556 alleles · rare exomes 1,282/1,460,212 · genomes 56/152,344 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.108%	927
Remaining individualsnot grpmax-eligible	0.0688%	1,453
Admixed American	0.0183%	5,457
African / African-American	0.0133%	7,502
Finnishnot grpmax-eligible	0.00469%	21,345

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.His28Pro
Coding: c.83A>C
MANE Select: NM_015932
dbSNP: rs140397494
Type: single nucleotide variant
Location: chr13:28662489 (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.Asn108His Uncertain significance ★★ ⚠ same condition
POMP p.Asn40Ser Uncertain significance ★★ ⚠ same condition
POMP p.Gln56His 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
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-his28pro (accessed [today's date]).

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