Is ZFPM2 p.Phe370= (c.1110C>T) pathogenic?

ZFPM2 p.Phe370= (c.1110C>T) is classified Likely benign in ZFPM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). Very rare (popmax 0.00223%, eas); Associated with 46,XY sex reversal 9.

What condition is associated with ZFPM2 p.Phe370= (c.1110C>T)?

ZFPM2 p.Phe370= (c.1110C>T) is associated with 46,XY sex reversal 9 (ClinVar).

How common is ZFPM2 p.Phe370= (c.1110C>T) in the general population?

ZFPM2 p.Phe370= (c.1110C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

ZFPM2 p.Phe370=

c.1110C>T · rs755422326 · VCV1592853

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6	GERP -3.7
Overall
CADD	5.476	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,848 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,613,954 alleles · very rare exomes 3/1,461,696 · genomes 0/152,258 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,848
South Asian	0.0022%	45,539

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.Phe370=
Coding: c.1110C>T
MANE Select: NM_012082
dbSNP: rs755422326
Type: single nucleotide variant
Location: chr8:105801192 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 51.93

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.Phe370Leu Uncertain significance ★ ⚠ same residue
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

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-phe370 (accessed [today's date]).

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