Is PSMC5 p.Ser253= (c.759C>T) pathogenic?

PSMC5 p.Ser253= (c.759C>T) is classified Likely benign in PSMC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-19). Very rare (popmax 0.0012%, sas).

How common is PSMC5 p.Ser253= (c.759C>T) in the general population?

PSMC5 p.Ser253= (c.759C>T) is very rare (popmax 0.0012%, sas) (gnomAD).

PSMC5 p.Ser253=

c.759C>T · VCV4936540

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0012%, sas)

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 0.026	GERP -4, phastCons 0.84
Overall
CADD	9.862	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0012% South Asian · 1/83,144 alleles

Overall 6.37e-05% 1/1,569,170 alleles · very rare exomes 1/1,416,914 · genomes 0/152,256 · joint denominator

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: PSMC5
Protein: p.Ser253=
Coding: c.759C>T
MANE Select: NM_002805
Type: single nucleotide variant
Location: chr17:63831115 (GRCh38)
Gene constraint: LOEUF 0.386 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.47 · 140 PDB
Residue 253: the 'may mediate interaction with prpf9' region; an α-helix

Full PSMC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSMC5 p.Pro320Arg Pathogenic/Likely pathogenic ★★ same type
PSMC5 c.264+9A>G Benign ★★ same type
PSMC5 c.97-8T>C Benign ★★ same type
PSMC5 p.Leu219= Benign ★★ same type
PSMC5 p.Leu280= Benign ★★ same type
PSMC5 p.Arg325Trp Pathogenic ★ same type
PSMC5 p.Met368Thr Likely pathogenic ★ ⚠ same type
PSMC5 c.1081-2A>G Uncertain significance ★ same type

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/psmc5-p-ser253 (accessed [today's date]).

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