Is PITRM1 p.Ser1005= (c.3015C>T) pathogenic?

PITRM1 p.Ser1005= (c.3015C>T) is classified Likely benign in PITRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-27). Ultra-rare (popmax 0.0164%, mid).

How common is PITRM1 p.Ser1005= (c.3015C>T) in the general population?

PITRM1 p.Ser1005= (c.3015C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PITRM1 p.Ser1005=

c.3015C>T · VCV4695407

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.57	donor gain · deltas
Constraint at this position
Conservation	phyloP 3.4	GERP 0.66, phastCons 1
Overall
CADD	16.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00639% 103/1,611,806 alleles · ultra-rare exomes 95/1,459,626 · genomes 8/152,180 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0563%	1,777
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0144%	6,934
East Asian	0.0134%	7,481
African / African-American	0.00534%	18,722
European (non-Finnish)	0.00357%	28,048
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594
South Asian	0.00329%	30,351
Admixed American	0.00167%	60,004

Finnish 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: PITRM1
Protein: p.Ser1005=
Coding: c.3015C>T
MANE Select: NM_014889
Type: single nucleotide variant
Location: chr10:3138240 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 8 PDB
Residue 1005: an α-helix

Full PITRM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PITRM1 p.Thr931Met Pathogenic/Likely pathogenic ★★ same type
PITRM1 p.Ala1003Thr Uncertain significance ★★ ⚠ same type
PITRM1 p.Ala559Val Uncertain significance ★★ ⚠ same type
PITRM1 p.Ala887Val Uncertain significance ★★ ⚠ same type
PITRM1 p.Ala942Val Uncertain significance ★★ ⚠ same type
PITRM1 p.Ala965Thr Uncertain significance ★★ ⚠ same type
PITRM1 p.Arg32Trp Uncertain significance ★★ ⚠ same type
PITRM1 p.Arg545Gln 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/pitrm1-p-ser1005 (accessed [today's date]).

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