Is PDCD5 p.Leu6Phe (c.16C>T) pathogenic?

PDCD5 p.Leu6Phe (c.16C>T) is classified Uncertain significance in PDCD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely pathogenic (0.7922); Ultra-rare (popmax 0.0214%, afr).

How common is PDCD5 p.Leu6Phe (c.16C>T) in the general population?

PDCD5 p.Leu6Phe (c.16C>T) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about PDCD5 p.Leu6Phe (c.16C>T)?

AlphaMissense predicts likely pathogenic (score 0.7922) — an in-silico prediction, not a clinical call.

PDCD5 p.Leu6Phe

c.16C>T · VCV3416106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7922 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7922	likely pathogenic
REVEL	0.412	indeterminate
SaProt	LLR -10.97	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 1.9	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 6,035 bp · p 0.72 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.0214% African / African-American · 15/70,148 alleles

Filtering AF 0.0131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00105% 16/1,528,600 alleles · ultra-rare exomes 8/1,376,518 · genomes 8/152,082 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,677
Remaining individualsnot grpmax-eligible	0.0017%	58,936

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.Leu6Phe
Coding: c.16C>T
MANE Select: NM_004708
Type: single nucleotide variant
Location: chr19:32581277 (GRCh38)
Gene constraint: LOEUF 1.837 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.13 · 3 PDB
Residue 6: an α-helix; the 'interaction with ppef1' region

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

Similar variants

PDCD5 c.105-7G>A Benign ★★ same type
PDCD5 p.Glu16Lys Benign ★★ ⚠ same type
PDCD5 p.Ala27Val Uncertain significance ★ ⚠ same type
PDCD5 p.Arg10Gly Uncertain significance ★ ⚠ same type
PDCD5 p.Arg53Gln Uncertain significance ★ ⚠ same type
PDCD5 p.Arg53Trp Uncertain significance ★ ⚠ same type
PDCD5 p.Asp122Tyr Uncertain significance ★ ⚠ same type
PDCD5 p.Gln101Arg 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-leu6phe (accessed [today's date]).

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