Is PDCD1 p.Val110Met (c.328G>A) pathogenic?

PDCD1 p.Val110Met (c.328G>A) is classified Uncertain significance in PDCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: ambiguous (0.3809); Very rare (popmax 0.005%, amr).

How common is PDCD1 p.Val110Met (c.328G>A) in the general population?

PDCD1 p.Val110Met (c.328G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about PDCD1 p.Val110Met (c.328G>A)?

AlphaMissense predicts ambiguous (score 0.3809) — an in-silico prediction, not a clinical call.

PDCD1 p.Val110Met

c.328G>A · VCV3887101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
AlphaMissense	0.3809	ambiguous
REVEL	0.305	indeterminate
SaProt	LLR -5.12	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3
Regional constraint	o/e 0.81	unconstrained · MANE · 6,129 bp · p 0.014 · regional, not allelic
Overall
CADD	16.24	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 0.005% Admixed American · 3/60,028 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00192% 31/1,613,930 alleles · very rare exomes 28/1,461,626 · genomes 3/152,304 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,009
East Asian	0.00446%	22,443
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.00186%	53,635
African / African-American	0.00133%	75,046
South Asian	0.0011%	91,088

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.Val110Met
Coding: c.328G>A
MANE Select: NM_005018
Type: single nucleotide variant
Location: chr2:241852729 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 74.53 · 38 PDB
Residue 110: 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-val110met (accessed [today's date]).

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