Is PDCD2L p.Ile264Phe (c.790A>T) pathogenic?

PDCD2L p.Ile264Phe (c.790A>T) is classified Uncertain significance in PDCD2L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: likely pathogenic (0.667); Absent from gnomAD v4.1.

How common is PDCD2L p.Ile264Phe (c.790A>T) in the general population?

PDCD2L p.Ile264Phe (c.790A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD2L p.Ile264Phe (c.790A>T)?

AlphaMissense predicts likely pathogenic (score 0.667) — an in-silico prediction, not a clinical call.

PDCD2L p.Ile264Phe

c.790A>T · VCV3929899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.667 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.667	likely pathogenic
REVEL	0.75	pathogenic-leaning
SaProt	LLR -9.49	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 22 kb · p 0.44 · regional, not allelic
Overall
CADD	26.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDCD2L
Protein: p.Ile264Phe
Coding: c.790A>T
MANE Select: NM_032346
Type: single nucleotide variant
Location: chr19:34413840 (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-ile264phe (accessed [today's date]).

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