Is ANKZF1 p.Arg448Pro (c.1343G>C) pathogenic?

ANKZF1 p.Arg448Pro (c.1343G>C) is classified Uncertain significance in ANKZF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-10). AlphaMissense: likely benign (0.1177); Absent from gnomAD v4.1.

How common is ANKZF1 p.Arg448Pro (c.1343G>C) in the general population?

ANKZF1 p.Arg448Pro (c.1343G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKZF1 p.Arg448Pro (c.1343G>C)?

AlphaMissense predicts likely benign (score 0.1177) — an in-silico prediction, not a clinical call.

ANKZF1 p.Arg448Pro

c.1343G>C · VCV3672384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1177 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1177	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.65	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 -0.7	GERP -4.6
Regional constraint	o/e 0.97	unconstrained · MANE · 6,184 bp · p 0.4 · regional, not allelic
Overall
CADD	0.059	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: ANKZF1
Protein: p.Arg448Pro
Coding: c.1343G>C
MANE Select: NM_018089
Type: single nucleotide variant
Location: chr2:219234964 (GRCh38)
Gene constraint: LOEUF 1.125 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.09
Residue 448: the 'disordered' region

Full ANKZF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKZF1 p.Arg448Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ANKZF1 p.Arg448Ter Uncertain significance ★ same residue
ANKZF1 p.Ala251Asp Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala269Thr Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala287Val Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala327Thr Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala391Val Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala486Thr 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/ankzf1-p-arg448pro (accessed [today's date]).

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