Is PITRM1 p.Val234Phe (c.700G>T) pathogenic?

PITRM1 p.Val234Phe (c.700G>T) is classified Uncertain significance in PITRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: ambiguous (0.3485); Ultra-rare (popmax 0.0825%, eas).

How common is PITRM1 p.Val234Phe (c.700G>T) in the general population?

PITRM1 p.Val234Phe (c.700G>T) is ultra-rare (popmax 0.0825%, eas) (gnomAD).

What do computational predictors say about PITRM1 p.Val234Phe (c.700G>T)?

AlphaMissense predicts ambiguous (score 0.3485) — an in-silico prediction, not a clinical call.

PITRM1 p.Val234Phe

c.700G>T · rs202132062 · VCV2395524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3485 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3485	ambiguous
REVEL	0.171	moderately benign-leaning
SaProt	LLR -11.16	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.51	GERP -3.1, phastCons 0.001
Regional constraint	o/e 1.12	unconstrained · MANE · 35 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	11.84	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 0.0825% East Asian · 37/44,848 alleles

Filtering AF 0.0615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.0138% 223/1,613,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.13%	771
East Asiangrpmax	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0384%	2,602
Admixed American	0.00668%	14,981
European (non-Finnish)	0.0061%	16,380
South Asian	0.0033%	30,301

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.Val234Phe
Coding: c.700G>T
MANE Select: NM_014889
dbSNP: rs202132062
Type: single nucleotide variant
Location: chr10:3163816 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 8 PDB
Residue 234: a disulfide bond

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-val234phe (accessed [today's date]).

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