Is PITRM1 p.Ter1038= (c.3113G>A) pathogenic?

PITRM1 p.Ter1038= (c.3113G>A) is classified Likely benign in PITRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). Ultra-rare (popmax 0.071%, afr).

How common is PITRM1 p.Ter1038= (c.3113G>A) in the general population?

PITRM1 p.Ter1038= (c.3113G>A) is ultra-rare (popmax 0.071%, afr) (gnomAD).

PITRM1 p.Ter1038=

c.3113G>A · rs374967739 · VCV1671282

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.071%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -3.5
Overall
CADD	0.986	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.071% African / African-American · 53/74,610 alleles

Filtering AF 0.0557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0503%

Overall 0.00589% 94/1,594,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.071%	1,408
Remaining individualsnot grpmax-eligible	0.0485%	2,062
Middle Eastern	0.0167%	5,998
Admixed American	0.00511%	19,585
European (non-Finnish)	0.0006%	166,764

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.Ter1038=
Coding: c.3113G>A
MANE Select: NM_014889
dbSNP: rs374967739
Type: single nucleotide variant
Location: chr10:3138032 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 8 PDB

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-ter1038 (accessed [today's date]).

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