Is PDCD1 p.His107= (c.321C>T) pathogenic?

PDCD1 p.His107= (c.321C>T) is classified Likely benign in PDCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). Very rare (popmax 0.000169%, nfe).

How common is PDCD1 p.His107= (c.321C>T) in the general population?

PDCD1 p.His107= (c.321C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

PDCD1 p.His107=

c.321C>T · VCV4534800

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.062	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP -3, phastCons 0.038
Overall
CADD	1.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,000 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,660 alleles · very rare

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.His107=
Coding: c.321C>T
MANE Select: NM_005018
Type: single nucleotide variant
Location: chr2:241852736 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 74.53 · 38 PDB
Residue 107: a β-strand; the ig-like v-type domain

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-his107 (accessed [today's date]).

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