Is PDCD1 p.Arg115His (c.344G>A) pathogenic?

PDCD1 p.Arg115His (c.344G>A) is classified Uncertain significance in PDCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely benign (0.1245); Very rare (popmax 0.00659%, sas).

How common is PDCD1 p.Arg115His (c.344G>A) in the general population?

PDCD1 p.Arg115His (c.344G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about PDCD1 p.Arg115His (c.344G>A)?

AlphaMissense predicts likely benign (score 0.1245) — an in-silico prediction, not a clinical call.

PDCD1 p.Arg115His

c.344G>A · rs777693230 · VCV2531224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1245 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1245	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3
Regional constraint	o/e 0.81	unconstrained · MANE · 6,129 bp · p 0.014 · regional, not allelic
Overall
CADD	10.47	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 0.00659% South Asian · 6/91,086 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00103% 15/1,461,468 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,181
Admixed American	0.005%	20,010
Remaining individualsnot grpmax-eligible	0.0016%	62,492
European (non-Finnish)	0.000424%	235,989

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.Arg115His
Coding: c.344G>A
MANE Select: NM_005018
dbSNP: rs777693230
Type: single nucleotide variant
Location: chr2:241852713 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 74.53 · 38 PDB
Residue 115: a disulfide bond; an α-helix; 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-arg115his (accessed [today's date]).

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