Is PDCD1 p.Val171Ala (c.512T>C) pathogenic?

PDCD1 p.Val171Ala (c.512T>C) is classified Uncertain significance in PDCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0944); Absent from gnomAD v4.1.

How common is PDCD1 p.Val171Ala (c.512T>C) in the general population?

PDCD1 p.Val171Ala (c.512T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD1 p.Val171Ala (c.512T>C)?

AlphaMissense predicts likely benign (score 0.0944) — an in-silico prediction, not a clinical call.

PDCD1 p.Val171Ala

c.512T>C · VCV3929843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0944 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0944	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -5.95	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 6.3	GERP 0.63, phastCons 0.75
Regional constraint	o/e 0.89	unconstrained · MANE · 1,258 bp · p 0.14 · regional, not allelic
Overall
CADD	11.7	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

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: PDCD1
Protein: p.Val171Ala
Coding: c.512T>C
MANE Select: NM_005018
Type: single nucleotide variant
Location: chr2:241852278 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 74.53 · 38 PDB

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-val171ala (accessed [today's date]).

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