Is SRY p.Ser191fs (c.570del) pathogenic?

SRY p.Ser191fs (c.570del) is classified Uncertain significance in SRY (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-02). No gnomAD frequency available for this variant; Associated with 46,XY sex reversal 1.

What condition is associated with SRY p.Ser191fs (c.570del)?

SRY p.Ser191fs (c.570del) is associated with 46,XY sex reversal 1 (ClinVar).

How common is SRY p.Ser191fs (c.570del) in the general population?

SRY p.Ser191fs (c.570del) is no gnomAD frequency available for this variant (gnomAD).

SRY p.Ser191fs

c.570del · rs1603308285 · VCV652674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

46,XY sex reversal 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6.4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SRY
Protein: p.Ser191fs
Coding: c.570del
MANE Select: NM_003140
dbSNP: rs1603308285
Type: Deletion
Location: chrY:2787034 (GRCh38)
Structure: AlphaFold pLDDT 69.01 · 10 PDB
Residue 191: the 'disordered' region

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

Disease context

46,XY sex reversal 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRY p.Met8fs Pathogenic ★ same condition
SRY p.Phe109fs Pathogenic same condition
SRY p.Arg76Leu Likely pathogenic ★★ same condition
SRY p.Ser155= Benign/Likely benign ★★ same condition
SRY p.Arg59fs Pathogenic ★ same condition
SRY p.Gln111Ter Pathogenic ★ same condition
SRY p.Gln57Ter Pathogenic ★ same condition
SRY p.Glu89fs Pathogenic ★ 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/sry-p-ser191fs (accessed [today's date]).

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