Is PITRM1 p.Ala397Val (c.1190C>T) pathogenic?

PITRM1 p.Ala397Val (c.1190C>T) is classified Benign in PITRM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1078); Common (popmax 71.2%, nfe) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about PITRM1 p.Ala397Val (c.1190C>T)?

AlphaMissense predicts likely benign (score 0.1078) — an in-silico prediction, not a clinical call.

PITRM1 p.Ala397Val

Q: How common is PITRM1 p.Ala397Val (c.1190C>T) in the general population?

PITRM1 p.Ala397Val (c.1190C>T) is common (popmax 71.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1190C>T · rs3182535 · VCV1545999

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1078 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 71.2%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1078	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.54, phastCons 0.93
Regional constraint	o/e 1.12	unconstrained · MANE · 35 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	19.94	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 71.2% European (non-Finnish) · 835,986/1,173,762 alleles

Filtering AF 71.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 71%

Overall 69.2% 1,112,257/1,606,552 alleles · common exomes 1,012,199/1,454,608 · genomes 100,058/151,944 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	71.2%	1
Finnishnot grpmax-eligible	69.4%	1
South Asian	68.2%	1
Remaining individualsnot grpmax-eligible	67.5%	1
Amishnot grpmax-eligible	66.3%	2
African / African-American	61.5%	2
Middle Eastern	59.9%	2
East Asian	59.2%	2
Ashkenazi Jewishnot grpmax-eligible	59.1%	2
Admixed American	56.6%	2

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.Ala397Val
Coding: c.1190C>T
MANE Select: NM_014889
dbSNP: rs3182535
Type: single nucleotide variant
Location: chr10:3158100 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 8 PDB
Residue 397: a UniProt-annotated variant site (in)

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-ala397val (accessed [today's date]).

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