Is PDCD6 p.Arg136Gln (c.407G>A) pathogenic?

PDCD6 p.Arg136Gln (c.407G>A) is classified Uncertain significance in PDCD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.1395); Ultra-rare (popmax 0.0111%, eas).

How common is PDCD6 p.Arg136Gln (c.407G>A) in the general population?

PDCD6 p.Arg136Gln (c.407G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about PDCD6 p.Arg136Gln (c.407G>A)?

AlphaMissense predicts likely benign (score 0.1395) — an in-silico prediction, not a clinical call.

PDCD6 p.Arg136Gln

c.407G>A · rs772846590 · VCV2381565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1395 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1395	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -10.61	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 7,910 bp · p 0.049 · regional, not allelic
Overall
CADD	24.1	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 0.0111% East Asian · 5/44,888 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.0013% 21/1,613,926 alleles · ultra-rare exomes 19/1,461,796 · genomes 2/152,130 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,978
African / African-American	0.00134%	74,902
European (non-Finnish)	0.00119%	84,286
South Asian	0.0011%	91,078

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: PDCD6
Protein: p.Arg136Gln
Coding: c.407G>A
MANE Select: NM_013232
dbSNP: rs772846590
Type: single nucleotide variant
Location: chr5:311332 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 90.08 · 10 PDB
Residue 136: the ef-hand 4 domain; an α-helix

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

Similar variants

PDCD6 p.Ala118Thr Uncertain significance ★ ⚠ same type
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PDCD6 p.Arg125Trp 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
PDCD6 p.Gln50Arg 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-arg136gln (accessed [today's date]).

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