Is POMP p.Pro76= (c.228G>A) pathogenic?

POMP p.Pro76= (c.228G>A) is classified Likely benign in POMP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-06). Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with POMP p.Pro76= (c.228G>A)?

POMP p.Pro76= (c.228G>A) is associated with Inborn genetic diseases (ClinVar).

How common is POMP p.Pro76= (c.228G>A) in the general population?

POMP p.Pro76= (c.228G>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

POMP p.Pro76=

c.228G>A · rs374762257 · VCV1614778

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.6	GERP -3.8
Overall
CADD	9.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,834 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00298% 48/1,612,456 alleles · ultra-rare exomes 40/1,460,236 · genomes 8/152,220 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,604
Remaining individualsnot grpmax-eligible	0.00961%	10,408
African / African-American	0.00934%	10,711
South Asian	0.00659%	15,174
European (non-Finnish)	0.00178%	56,124

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.Pro76=
Coding: c.228G>A
MANE Select: NM_015932
dbSNP: rs374762257
Type: single nucleotide variant
Location: chr13:28668538 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 81.76 · 11 PDB
Residue 76: an α-helix

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.Pro76Ser Uncertain significance ★★ ⚠ same residue
POMP p.Pro76Leu Uncertain significance ★★ ⚠ same residue
POMP p.Pro76Thr 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

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-pro76 (accessed [today's date]).

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