Is PITRM1 p.Val330Phe (c.988G>T) pathogenic?

PITRM1 p.Val330Phe (c.988G>T) is classified Uncertain significance in PITRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely benign (0.1537); Very rare (popmax 0.00447%, eas).

How common is PITRM1 p.Val330Phe (c.988G>T) in the general population?

PITRM1 p.Val330Phe (c.988G>T) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about PITRM1 p.Val330Phe (c.988G>T)?

AlphaMissense predicts likely benign (score 0.1537) — an in-silico prediction, not a clinical call.

PITRM1 p.Val330Phe

c.988G>T · rs202233012 · VCV3213303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1537 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1537	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -11.51	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.62	GERP -0.26, phastCons 0.1
Regional constraint	o/e 1.12	unconstrained · MANE · 35 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	15.22	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 0.00447% East Asian · 2/44,708 alleles

Filtering AF 0.000742% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000138% 2/1,447,858 alleles · very rare

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.Val330Phe
Coding: c.988G>T
MANE Select: NM_014889
dbSNP: rs202233012
Type: single nucleotide variant
Location: chr10:3159867 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 8 PDB
Residue 330: a disulfide bond; a β-strand

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

Similar variants

PITRM1 p.Val330Ile 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-val330phe (accessed [today's date]).

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