Is ZFPM2 p.Asp95= (c.285C>T) pathogenic?

ZFPM2 p.Asp95= (c.285C>T) is classified Likely benign in ZFPM2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-01). Ultra-rare (popmax 0.0329%, mid); Associated with 46,XY sex reversal 9.

What condition is associated with ZFPM2 p.Asp95= (c.285C>T)?

ZFPM2 p.Asp95= (c.285C>T) is associated with 46,XY sex reversal 9 (ClinVar).

How common is ZFPM2 p.Asp95= (c.285C>T) in the general population?

ZFPM2 p.Asp95= (c.285C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

ZFPM2 p.Asp95=

c.285C>T · rs371910925 · VCV696378

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.8	GERP -3.8
Overall
CADD	0.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.00937% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00751%

Overall 0.0146% 236/1,611,264 alleles · ultra-rare exomes 215/1,459,124 · genomes 21/152,140 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.329%	304
Remaining individualsnot grpmax-eligible	0.0401%	2,494
Middle Easterngrpmax	0.0329%	3,041
Admixed American	0.0167%	5,980
South Asian	0.0155%	6,452
African / African-American	0.00801%	12,480
European (non-Finnish)	0.00687%	14,551
East Asian	0.00223%	44,830

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp95=
Coding: c.285C>T
MANE Select: NM_012082
dbSNP: rs371910925
Type: single nucleotide variant
Location: chr8:105444365 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 51.93
Residue 95: the 'disordered' region

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

Similar variants

ZFPM2 p.Arg117Gln Uncertain significance ★★ ⚠ same condition
ZFPM2 p.Asn136Ser Uncertain significance ★★ ⚠ same condition
ZFPM2 p.Asp96Tyr Uncertain significance ★★ ⚠ same condition
ZFPM2 p.Gln707Glu Uncertain significance ★★ ⚠ same condition
ZFPM2 p.Gly164Arg Uncertain significance ★★ ⚠ same condition
ZFPM2 p.Gly531Asp Uncertain significance ★★ ⚠ same condition
ZFPM2 p.Gly547Arg Uncertain significance ★★ ⚠ same condition
ZFPM2 p.His699Pro 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/zfpm2-p-asp95 (accessed [today's date]).

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