Is ZFPM2 p.Ser388= (c.1164C>T) pathogenic?

ZFPM2 p.Ser388= (c.1164C>T) is classified Likely benign in ZFPM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-18). Ultra-rare (popmax 0.045%, amr); Associated with 46,XY sex reversal 9.

What condition is associated with ZFPM2 p.Ser388= (c.1164C>T)?

ZFPM2 p.Ser388= (c.1164C>T) is associated with 46,XY sex reversal 9 (ClinVar).

How common is ZFPM2 p.Ser388= (c.1164C>T) in the general population?

ZFPM2 p.Ser388= (c.1164C>T) is ultra-rare (popmax 0.045%, amr) (gnomAD).

ZFPM2 p.Ser388=

c.1164C>T · rs376392532 · VCV414007

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

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 -3.2	GERP -3.7
Overall
CADD	5.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.045% Admixed American · 27/60,016 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00347% 56/1,613,944 alleles · ultra-rare exomes 47/1,461,692 · genomes 9/152,252 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.0022%	45,380
African / African-American	0.00133%	75,044

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.Ser388=
Coding: c.1164C>T
MANE Select: NM_012082
dbSNP: rs376392532
Type: single nucleotide variant
Location: chr8:105801246 (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.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-ser388 (accessed [today's date]).

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