Is ANKRD50 p.Phe455Ile (c.1363T>A) pathogenic?

ANKRD50 p.Phe455Ile (c.1363T>A) is classified Uncertain significance in ANKRD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: likely pathogenic (0.8271); Absent from gnomAD v4.1.

How common is ANKRD50 p.Phe455Ile (c.1363T>A) in the general population?

ANKRD50 p.Phe455Ile (c.1363T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD50 p.Phe455Ile (c.1363T>A)?

AlphaMissense predicts likely pathogenic (score 0.8271) — an in-silico prediction, not a clinical call.

ANKRD50 p.Phe455Ile

c.1363T>A · VCV3398917

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8271 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8271	likely pathogenic
REVEL	0.438	indeterminate
SaProt	LLR -7.26	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.4	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 40 kb · p 3.5e-10 · regional, not allelic
Overall
CADD	24.5	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: ANKRD50
Protein: p.Phe455Ile
Coding: c.1363T>A
MANE Select: NM_020337
Type: single nucleotide variant
Location: chr4:124671914 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.26

Full ANKRD50 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD50 p.Ala1053Val Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala1081Gly Uncertain significance ★ same type
ANKRD50 p.Ala1201Ser Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala1277Val Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala219Asp Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala372Thr Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala437Val Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala469Val 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/ankrd50-p-phe455ile (accessed [today's date]).

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