Is PDCD1 p.Ser285Phe (c.854C>T) pathogenic?

PDCD1 p.Ser285Phe (c.854C>T) is classified Uncertain significance in PDCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.3393); Rare (popmax 0.106%, sas).

How common is PDCD1 p.Ser285Phe (c.854C>T) in the general population?

PDCD1 p.Ser285Phe (c.854C>T) is rare (popmax 0.106%, sas) (gnomAD).

What do computational predictors say about PDCD1 p.Ser285Phe (c.854C>T)?

AlphaMissense predicts likely benign (score 0.3393) — an in-silico prediction, not a clinical call.

PDCD1 p.Ser285Phe

c.854C>T · VCV4566153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3393 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.106%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3393	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -8.29	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 5.4	GERP 0.18, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,258 bp · p 0.14 · regional, not allelic
Overall
CADD	24.1	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 0.106% South Asian · 96/90,888 alleles

Filtering AF 0.0885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0821%

Overall 0.00633% 102/1,611,838 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.106%	947
Middle Eastern	0.0167%	6,006
Remaining individualsnot grpmax-eligible	0.00641%	15,601
European (non-Finnish)	8.48e-05%	1,179,244

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: PDCD1
Protein: p.Ser285Phe
Coding: c.854C>T
MANE Select: NM_005018
Type: single nucleotide variant
Location: chr2:241851071 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 74.53 · 38 PDB
Residue 285: the 'disordered' region

Full PDCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDCD1 c.437-115G>A Benign ★★ same type
PDCD1 c.593-56C>G Benign ★★ same type
PDCD1 c.627+189G>A Benign ★★ same type
PDCD1 c.628-110A>G Benign ★★ same type
PDCD1 c.76+126G>C Benign ★★ same type
PDCD1 c.76+15C>T Benign ★★ same type
PDCD1 c.*889G>A Benign ★★ same type
PDCD1 p.Ala215Val Benign ★★ 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/pdcd1-p-ser285phe (accessed [today's date]).

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