Is PITRM1 p.Leu883Phe (c.2647C>T) pathogenic?

PITRM1 p.Leu883Phe (c.2647C>T) is classified Benign/Likely benign in PITRM1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-01). AlphaMissense: ambiguous (0.409); Rare (popmax 0.89%, nfe).

How common is PITRM1 p.Leu883Phe (c.2647C>T) in the general population?

PITRM1 p.Leu883Phe (c.2647C>T) is rare (popmax 0.89%, nfe) (gnomAD).

What do computational predictors say about PITRM1 p.Leu883Phe (c.2647C>T)?

AlphaMissense predicts ambiguous (score 0.409) — an in-silico prediction, not a clinical call.

PITRM1 p.Leu883Phe

c.2647C>T · rs71477812 · VCV684532

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.409 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.89%, nfe)

Computational evidence

Protein change
AlphaMissense	0.409	ambiguous
REVEL	0.523	indeterminate
SaProt	LLR -10.92	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 35 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	26.0	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 0.89% European (non-Finnish) · 10,311/1,158,228 alleles

Filtering AF 0.876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.87%

Overall 0.831% 13,088/1,575,590 alleles · rare exomes 11,981/1,423,332 · genomes 1,107/152,258 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.88%	53
Ashkenazi Jewishnot grpmax-eligible	1.31%	76
Remaining individualsnot grpmax-eligible	0.916%	109
European (non-Finnish)grpmax	0.89%	112
Admixed American	0.675%	148
Middle Eastern	0.631%	159
Amishnot grpmax-eligible	0.329%	304
South Asian	0.19%	527
African / African-American	0.14%	714
East Asian	0.00229%	43,698

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.Leu883Phe
Coding: c.2647C>T
MANE Select: NM_014889
dbSNP: rs71477812
Type: single nucleotide variant
Location: chr10:3140811 (GRCh38)
Gene constraint: LOEUF 0.997 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 8 PDB
Residue 883: an α-helix

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-leu883phe (accessed [today's date]).

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