Is PITRM1 p.Arg599Trp (c.1795C>T) pathogenic?

PITRM1 p.Arg599Trp (c.1795C>T) is classified Uncertain significance in PITRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: likely benign (0.2779); Rare (popmax 0.161%, eas).

How common is PITRM1 p.Arg599Trp (c.1795C>T) in the general population?

PITRM1 p.Arg599Trp (c.1795C>T) is rare (popmax 0.161%, eas) (gnomAD).

What do computational predictors say about PITRM1 p.Arg599Trp (c.1795C>T)?

AlphaMissense predicts likely benign (score 0.2779) — an in-silico prediction, not a clinical call.

PITRM1 p.Arg599Trp

c.1795C>T · rs564844894 · VCV3213284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2779 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.161%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2779	likely benign
REVEL	0.524	indeterminate
SaProt	LLR -12.57	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -0.61, phastCons 0.99
Regional constraint	o/e 1.12	unconstrained · MANE · 35 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.161% East Asian · 72/44,820 alleles

Filtering AF 0.131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.0067% 108/1,611,490 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.161%	622
African / African-American	0.0107%	9,360
Remaining individualsnot grpmax-eligible	0.00481%	20,798
Admixed American	0.00336%	29,725
South Asian	0.00221%	45,176
European (non-Finnish)	0.00178%	56,152

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.Arg599Trp
Coding: c.1795C>T
MANE Select: NM_014889
dbSNP: rs564844894
Type: single nucleotide variant
Location: chr10:3149697 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 8 PDB
Residue 599: a β-strand

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

Similar variants

PREP p.Tyr599Phe Uncertain significance ★ ⚠ same residue
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

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-arg599trp (accessed [today's date]).

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