Is ADK p.Pro52Leu (c.155C>T) pathogenic?

ADK p.Pro52Leu (c.155C>T) is classified Uncertain significance in ADK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1785); Very rare (popmax 0.000848%, nfe).

How common is ADK p.Pro52Leu (c.155C>T) in the general population?

ADK p.Pro52Leu (c.155C>T) is very rare (popmax 0.000848%, nfe) (gnomAD).

What do computational predictors say about ADK p.Pro52Leu (c.155C>T)?

AlphaMissense predicts likely benign (score 0.1785) — an in-silico prediction, not a clinical call.

ADK p.Pro52Leu

c.155C>T · rs1844455477 · VCV1408446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1785 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1785	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -12.00	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 557 kb · p 4.5e-07 · regional, not allelic
Overall
CADD	22.0	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 0.000848% European (non-Finnish) · 10/1,179,660 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000684% 10/1,461,292 alleles · very rare

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: ADK
Protein: p.Pro52Leu
Coding: c.155C>T
MANE Select: NM_006721
dbSNP: rs1844455477
Type: single nucleotide variant
Location: chr10:74224552 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.40 · 7 PDB
Residue 52: a β-strand

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

Similar variants

ADK p.Ala344Val Pathogenic/Likely pathogenic ★★ same type
ADK p.Arg338Cys Uncertain significance ★★ ⚠ same type
ADK p.Arg338His Uncertain significance ★★ ⚠ same type
ADK p.Asn53Asp Uncertain significance ★★ ⚠ same type
ADK p.Asp305Glu Uncertain significance ★★ ⚠ same type
ADK p.Gln306Leu Uncertain significance ★★ ⚠ same type
ADK p.Ile87Val Uncertain significance ★★ ⚠ same type
ADK p.Lys264Asn 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/adk-p-pro52leu (accessed [today's date]).

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