Is PDCD5 p.Ala27Val (c.80C>T) pathogenic?

PDCD5 p.Ala27Val (c.80C>T) is classified Uncertain significance in PDCD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0869); Rare (popmax 0.111%, afr).

How common is PDCD5 p.Ala27Val (c.80C>T) in the general population?

PDCD5 p.Ala27Val (c.80C>T) is rare (popmax 0.111%, afr) (gnomAD).

What do computational predictors say about PDCD5 p.Ala27Val (c.80C>T)?

AlphaMissense predicts likely benign (score 0.0869) — an in-silico prediction, not a clinical call.

PDCD5 p.Ala27Val

c.80C>T · rs200484934 · VCV2376275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0869 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0869	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -9.14	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 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 6,035 bp · p 0.72 · regional, not allelic
Overall
CADD	23.1	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 0.111% African / African-American · 83/74,842 alleles

Filtering AF 0.0916% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0845%

Overall 0.00688% 111/1,612,214 alleles · rare exomes 56/1,460,252 · genomes 55/151,962 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.111%	902
Admixed American	0.02%	4,991
Remaining individualsnot grpmax-eligible	0.0192%	5,203
Middle Eastern	0.0165%	6,050
South Asian	0.0033%	30,296

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: PDCD5
Protein: p.Ala27Val
Coding: c.80C>T
MANE Select: NM_004708
dbSNP: rs200484934
Type: single nucleotide variant
Location: chr19:32582208 (GRCh38)
Gene constraint: LOEUF 1.837 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.13 · 3 PDB
Residue 27: an α-helix; the 'interaction with ppef1' region; the 'disordered' region

Full PDCD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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PDCD5 p.Arg53Trp Uncertain significance ★ ⚠ same type
PDCD5 p.Asp122Tyr Uncertain significance ★ ⚠ same type
PDCD5 p.Gln101Arg Uncertain significance ★ ⚠ same type
PDCD5 p.Ile93Val Uncertain significance ★ ⚠ 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/pdcd5-p-ala27val (accessed [today's date]).

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