Is PDCD2L p.Pro7Leu (c.20C>T) pathogenic?

PDCD2L p.Pro7Leu (c.20C>T) is classified Uncertain significance in PDCD2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). AlphaMissense: ambiguous (0.3645); Very rare (popmax 0.00733%, nfe).

How common is PDCD2L p.Pro7Leu (c.20C>T) in the general population?

PDCD2L p.Pro7Leu (c.20C>T) is very rare (popmax 0.00733%, nfe) (gnomAD).

What do computational predictors say about PDCD2L p.Pro7Leu (c.20C>T)?

AlphaMissense predicts ambiguous (score 0.3645) — an in-silico prediction, not a clinical call.

PDCD2L p.Pro7Leu

c.20C>T · VCV3416091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3645 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00733%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3645	ambiguous
REVEL	0.12	moderately benign-leaning
SaProt	LLR -10.86	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.98	GERP 0.73
Regional constraint	o/e 1.04	unconstrained · MANE · 22 kb · p 0.44 · regional, not allelic
Overall
CADD	19.61	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 0.00733% European (non-Finnish) · 84/1,145,630 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00609% 94/1,544,382 alleles · very rare exomes 83/1,392,128 · genomes 11/152,254 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00733%	13,638
African / African-American	0.00549%	18,231
Remaining individualsnot grpmax-eligible	0.00502%	19,934
East Asian	0.00489%	20,434
South Asian	0.00119%	83,904

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.Pro7Leu
Coding: c.20C>T
MANE Select: NM_032346
Type: single nucleotide variant
Location: chr19:34404450 (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-pro7leu (accessed [today's date]).

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