Is POMP p.Leu57= (c.171C>T) pathogenic?

POMP p.Leu57= (c.171C>T) is classified Likely benign in POMP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-23). Ultra-rare (popmax 0.0134%, afr).

How common is POMP p.Leu57= (c.171C>T) in the general population?

POMP p.Leu57= (c.171C>T) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

POMP p.Leu57=

c.171C>T · rs368393514 · VCV1632826

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

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 1.1	GERP 0.98, phastCons 1
Overall
CADD	9.782	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% African / African-American · 10/74,814 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00551%

Overall 0.000623% 10/1,605,332 alleles · ultra-rare exomes 2/1,453,072 · genomes 8/152,260 · 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.Leu57=
Coding: c.171C>T
MANE Select: NM_015932
dbSNP: rs368393514
Type: single nucleotide variant
Location: chr13:28668481 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 81.76 · 11 PDB
Residue 57: an α-helix

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

Similar variants

POMP p.Leu57Pro 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-leu57 (accessed [today's date]).

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