Is PDCD2L p.Cys82Phe (c.245G>T) pathogenic?

PDCD2L p.Cys82Phe (c.245G>T) is classified Uncertain significance in PDCD2L (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely benign (0.0748); Very rare (popmax 0.00722%, nfe).

How common is PDCD2L p.Cys82Phe (c.245G>T) in the general population?

PDCD2L p.Cys82Phe (c.245G>T) is very rare (popmax 0.00722%, nfe) (gnomAD).

What do computational predictors say about PDCD2L p.Cys82Phe (c.245G>T)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

PDCD2L p.Cys82Phe

c.245G>T · rs762224956 · VCV2463725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00722%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.66	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 0.43	GERP -4.5
Regional constraint	o/e 1.04	unconstrained · MANE · 22 kb · p 0.44 · regional, not allelic
Overall
CADD	8.004	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00722% European (non-Finnish) · 85/1,177,596 alleles

Filtering AF 0.00597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00548% 88/1,605,834 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00722%	13,854
East Asian	0.00224%	44,572
Finnishnot grpmax-eligible	0.00164%	60,914
African / African-American	0.00134%	74,832

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: PDCD2L
Protein: p.Cys82Phe
Coding: c.245G>T
MANE Select: NM_032346
dbSNP: rs762224956
Type: single nucleotide variant
Location: chr19:34404785 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.93

Full PDCD2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDCD2L p.Ala111Val Uncertain significance ★ ⚠ same type
PDCD2L p.Ala174Thr Uncertain significance ★ ⚠ same type
PDCD2L p.Ala175Val Uncertain significance ★ ⚠ same type
PDCD2L p.Ala258Val Uncertain significance ★ ⚠ same type
PDCD2L p.Ala2Val Uncertain significance ★ ⚠ same type
PDCD2L p.Ala38Ser Uncertain significance ★ ⚠ same type
PDCD2L p.Ala44Ser Uncertain significance ★ ⚠ same type
PDCD2L p.Ala81Thr 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/pdcd2l-p-cys82phe (accessed [today's date]).

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