Is ANKRD33B p.Arg119Pro (c.356G>C) pathogenic?

ANKRD33B p.Arg119Pro (c.356G>C) is classified Uncertain significance in ANKRD33B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely benign (0.223); Absent from gnomAD v4.1.

How common is ANKRD33B p.Arg119Pro (c.356G>C) in the general population?

ANKRD33B p.Arg119Pro (c.356G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD33B p.Arg119Pro (c.356G>C)?

AlphaMissense predicts likely benign (score 0.223) — an in-silico prediction, not a clinical call.

ANKRD33B p.Arg119Pro

c.356G>C · rs1218793103 · VCV2319231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.223 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.223	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.66	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 7.3	GERP -1.1, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 47 bp · p 0.00022 · regional, not allelic
Overall
CADD	28.6	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

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: ANKRD33B
Protein: p.Arg119Pro
Coding: c.356G>C
MANE Select: NM_001164440
dbSNP: rs1218793103
Type: single nucleotide variant
Location: chr5:10564823 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 67.74

Full ANKRD33B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD33B p.Arg119Ser Uncertain significance ★ ⚠ same residue
ANKRD33B p.Asp301Asn Uncertain significance ★★ ⚠ same type
ANKRD33B p.Ala158Pro Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala168Val Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala214Val Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala274Thr Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala319Val Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala348Val 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/ankrd33b-p-arg119pro (accessed [today's date]).

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