Is PDCD6 p.Phe188Val (c.562T>G) pathogenic?

PDCD6 p.Phe188Val (c.562T>G) is classified Uncertain significance in PDCD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely pathogenic (0.9282); Absent from gnomAD v4.1.

How common is PDCD6 p.Phe188Val (c.562T>G) in the general population?

PDCD6 p.Phe188Val (c.562T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD6 p.Phe188Val (c.562T>G)?

AlphaMissense predicts likely pathogenic (score 0.9282) — an in-silico prediction, not a clinical call.

PDCD6 p.Phe188Val

c.562T>G · VCV4133634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9282 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9282	likely pathogenic
REVEL	0.428	indeterminate
SaProt	LLR -11.16	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 7,910 bp · p 0.049 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: PDCD6
Protein: p.Phe188Val
Coding: c.562T>G
MANE Select: NM_013232
Type: single nucleotide variant
Location: chr5:314501 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 90.08 · 10 PDB
Residue 188: an α-helix; the ef-hand 5 domain

Full PDCD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDCD6 p.Ala118Thr Uncertain significance ★ ⚠ same type
PDCD6 p.Arg100Cys Uncertain significance ★ ⚠ same type
PDCD6 p.Arg125Trp Uncertain significance ★ ⚠ same type
PDCD6 p.Arg136Gln Uncertain significance ★ ⚠ same type
PDCD6 p.Asn54Lys Uncertain significance ★ ⚠ same type
PDCD6 p.Asn54Ser Uncertain significance ★ ⚠ same type
PDCD6 p.Asp139Gly Uncertain significance ★ ⚠ same type
PDCD6 p.Cys155Phe 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/pdcd6-p-phe188val (accessed [today's date]).

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