Is ANKRD33B p.Cys286Phe (c.857G>T) pathogenic?

ANKRD33B p.Cys286Phe (c.857G>T) is classified Likely benign in ANKRD33B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.0658); Absent from gnomAD v4.1.

How common is ANKRD33B p.Cys286Phe (c.857G>T) in the general population?

ANKRD33B p.Cys286Phe (c.857G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD33B p.Cys286Phe (c.857G>T)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

ANKRD33B p.Cys286Phe

c.857G>T · rs1737273307 · VCV3125829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.04	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 1.3	GERP -3.4, phastCons 0.8
Regional constraint	o/e 0.96	unconstrained · MANE · 85 kb · p 0.32 · regional, not allelic
Overall
CADD	2.241	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

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.Cys286Phe
Coding: c.857G>T
MANE Select: NM_001164440
dbSNP: rs1737273307
Type: single nucleotide variant
Location: chr5:10649485 (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.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
ANKRD33B p.Ala350Val 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-cys286phe (accessed [today's date]).

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