Is PISD p.Pro37= (c.111C>T) pathogenic?

PISD p.Pro37= (c.111C>T) is classified Likely benign in PISD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). Very rare (popmax 0.00773%, amr).

How common is PISD p.Pro37= (c.111C>T) in the general population?

PISD p.Pro37= (c.111C>T) is very rare (popmax 0.00773%, amr) (gnomAD).

PISD p.Pro37=

c.111C>T · rs540456265 · VCV2896836

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00773%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.015	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 2.8, phastCons 1
Overall
CADD	1.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00773% Admixed American · 4/51,768 alleles

Filtering AF 0.00586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00539%

Overall 0.00649% 101/1,556,220 alleles · very rare exomes 87/1,403,972 · genomes 14/152,248 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0417%	2,398
Admixed Americangrpmax	0.00773%	12,942
European (non-Finnish)	0.00713%	14,021
Remaining individualsnot grpmax-eligible	0.00331%	30,193
African / African-American	0.00136%	73,460

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: PISD
Protein: p.Pro37=
Coding: c.111C>T
MANE Select: NM_001326411
dbSNP: rs540456265
Type: single nucleotide variant
Location: chr22:31650733 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.13
Residue 37: the 'necessary for localization to both lipid droplets and mitochondria' region

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

Similar variants

PISD p.Cys300Tyr Pathogenic/Likely pathogenic ★★ same type
PISD p.Ala234Val Uncertain significance ★★ ⚠ same type
PISD p.Ala386Val Uncertain significance ★★ ⚠ same type
PISD p.Arg125Cys Uncertain significance ★★ ⚠ same type
PISD p.Arg125His Uncertain significance ★★ ⚠ same type
PISD p.Arg136His Uncertain significance ★★ ⚠ same type
PISD p.Arg163Cys Uncertain significance ★★ ⚠ same type
PISD p.Arg163His 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/pisd-p-pro37 (accessed [today's date]).

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