Is ANKRD50 p.Arg387Pro (c.1160G>C) pathogenic?

ANKRD50 p.Arg387Pro (c.1160G>C) is classified Uncertain significance in ANKRD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: likely pathogenic (0.8134); Very rare (popmax 8.48e-05%, nfe).

How common is ANKRD50 p.Arg387Pro (c.1160G>C) in the general population?

ANKRD50 p.Arg387Pro (c.1160G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ANKRD50 p.Arg387Pro (c.1160G>C)?

AlphaMissense predicts likely pathogenic (score 0.8134) — an in-silico prediction, not a clinical call.

ANKRD50 p.Arg387Pro

c.1160G>C · VCV3917292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8134 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8134	likely pathogenic
REVEL	0.28	benign-leaning
SaProt	LLR -10.68	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 40 kb · p 3.5e-10 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,828 alleles

Overall 6.2e-05% 1/1,613,832 alleles · very rare exomes 1/1,461,622 · genomes 0/152,210 · joint denominator

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: ANKRD50
Protein: p.Arg387Pro
Coding: c.1160G>C
MANE Select: NM_020337
Type: single nucleotide variant
Location: chr4:124672117 (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.Arg387Leu Uncertain significance ★ ⚠ same residue
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

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-arg387pro (accessed [today's date]).

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