Is PDCD11 p.Ser397Arg (c.1189A>C) pathogenic?

PDCD11 p.Ser397Arg (c.1189A>C) is classified Uncertain significance in PDCD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely benign (0.2348); Ultra-rare (popmax 0.0219%, amr).

How common is PDCD11 p.Ser397Arg (c.1189A>C) in the general population?

PDCD11 p.Ser397Arg (c.1189A>C) is ultra-rare (popmax 0.0219%, amr) (gnomAD).

What do computational predictors say about PDCD11 p.Ser397Arg (c.1189A>C)?

AlphaMissense predicts likely benign (score 0.2348) — an in-silico prediction, not a clinical call.

PDCD11 p.Ser397Arg

c.1189A>C · rs753444652 · VCV3210524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2348 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0219%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2348	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -6.10	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 4.7	GERP 0.34, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 47 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	19.95	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 0.0219% Admixed American · 13/59,364 alleles

Filtering AF 0.0129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0103%

Overall 0.000869% 14/1,610,330 alleles · ultra-rare exomes 4/1,458,106 · genomes 10/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0219%	4,566
Remaining individualsnot grpmax-eligible	0.0016%	62,316

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: PDCD11
Protein: p.Ser397Arg
Coding: c.1189A>C
MANE Select: NM_014976
dbSNP: rs753444652
Type: single nucleotide variant
Location: chr10:103413969 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.40 · 1 PDB
Residue 397: a UniProt-annotated variant site (in); the s1 motif 4 domain

Full PDCD11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDCD11 p.Ala1131Gly Uncertain significance ★ ⚠ same type
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PDCD11 p.Ala1526Gly Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1526Thr Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1538Thr Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1594Val Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1605Glu Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1605Thr 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/pdcd11-p-ser397arg (accessed [today's date]).

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