Is PRAME p.Pro82Ser (c.244C>T) pathogenic?

PRAME p.Pro82Ser (c.244C>T) is classified Uncertain significance in PRAME (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: ambiguous (0.553); Very rare (popmax 0.00619%, nfe).

How common is PRAME p.Pro82Ser (c.244C>T) in the general population?

PRAME p.Pro82Ser (c.244C>T) is very rare (popmax 0.00619%, nfe) (gnomAD).

What do computational predictors say about PRAME p.Pro82Ser (c.244C>T)?

AlphaMissense predicts ambiguous (score 0.553) — an in-silico prediction, not a clinical call.

PRAME p.Pro82Ser

c.244C>T · VCV3424439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.553 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00619%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.553	ambiguous
REVEL	0.152	moderately benign-leaning
SaProt	LLR -11.29	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 8,762 bp · p 0.25 · regional, not allelic
Overall
CADD	23.1	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 0.00619% European (non-Finnish) · 73/1,179,890 alleles

Filtering AF 0.00503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00462%

Overall 0.00465% 75/1,613,656 alleles · very rare exomes 72/1,461,718 · genomes 3/151,938 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00619%	16,163
African / African-American	0.00267%	37,432

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: PRAME
Protein: p.Pro82Ser
Coding: c.244C>T
MANE Select: NM_206956
Type: single nucleotide variant
Location: chr22:22550867 (GRCh38)

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

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/prame-p-pro82ser (accessed [today's date]).

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