Is POMP p.Glu49Gln (c.145G>C) pathogenic?

POMP p.Glu49Gln (c.145G>C) is classified Uncertain significance in POMP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-19). AlphaMissense: likely benign (0.1858); Very rare (popmax 6.41e-05%).

How common is POMP p.Glu49Gln (c.145G>C) in the general population?

POMP p.Glu49Gln (c.145G>C) is very rare (popmax 6.41e-05%) (gnomAD).

What do computational predictors say about POMP p.Glu49Gln (c.145G>C)?

AlphaMissense predicts likely benign (score 0.1858) — an in-silico prediction, not a clinical call.

POMP p.Glu49Gln

c.145G>C · rs779225629 · VCV3003034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1858 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.41e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1858	likely benign
REVEL	0.603	indeterminate
SaProt	LLR -9.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 19 kb · p 0.048 · regional, not allelic
Overall
CADD	24.8	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 6.41e-05%

Overall 6.41e-05% 1/1,559,016 alleles · very rare exomes 1/1,408,208 · genomes 0/150,808 · 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.Glu49Gln
Coding: c.145G>C
MANE Select: NM_015932
dbSNP: rs779225629
Type: single nucleotide variant
Location: chr13:28664552 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 81.76 · 11 PDB
Residue 49: an α-helix

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

Similar variants

POMP p.Glu49Gly Uncertain significance ★ ⚠ same residue
POMP p.Arg32Gln Uncertain significance ★★ ⚠ same type
POMP p.Arg32Trp Uncertain significance ★★ ⚠ same type
POMP p.Asn108His Uncertain significance ★★ ⚠ same type
POMP p.Asn40Ser Uncertain significance ★★ ⚠ same type
POMP p.Gln56His Uncertain significance ★★ ⚠ same type
POMP p.His28Pro Uncertain significance ★★ ⚠ same type
POMP p.Ile112Val Uncertain significance ★★ ⚠ 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/pomp-p-glu49gln (accessed [today's date]).

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