Is ZFPM2 p.Pro592= (c.1776T>C) pathogenic?

ZFPM2 p.Pro592= (c.1776T>C) is classified Benign in ZFPM2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 13.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with 46,XY sex reversal 9.

What condition is associated with ZFPM2 p.Pro592= (c.1776T>C)?

ZFPM2 p.Pro592= (c.1776T>C) is associated with 46,XY sex reversal 9 (ClinVar).

ZFPM2 p.Pro592=

Q: How common is ZFPM2 p.Pro592= (c.1776T>C) in the general population?

ZFPM2 p.Pro592= (c.1776T>C) is common (popmax 13.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1776T>C · rs16873732 · VCV260172

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 13.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

46,XY sex reversal 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -6.2	GERP -3.7
Overall
CADD	0.661	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.8% African / African-American · 10,352/75,006 alleles

Filtering AF 13.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.5%

Overall 2.98% 48,047/1,613,916 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.8%	7
Ashkenazi Jewishnot grpmax-eligible	7.02%	14
Admixed American	3.8%	26
Remaining individualsnot grpmax-eligible	3.78%	26
Middle Eastern	3.3%	30
South Asian	3.02%	33
European (non-Finnish)	2.33%	43
Finnishnot grpmax-eligible	0.526%	190
East Asian	0.495%	202
Amishnot grpmax-eligible	0.439%	228

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: ZFPM2
Protein: p.Pro592=
Coding: c.1776T>C
dbSNP: rs16873732
Type: single nucleotide variant
Location: chr8:105801858 (GRCh38)

Full ZFPM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

46,XY sex reversal 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/zfpm2-p-pro592 (accessed [today's date]).

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