Is ADCK2 p.Pro85Ala (c.253C>G) pathogenic?

ADCK2 p.Pro85Ala (c.253C>G) is classified Uncertain significance in ADCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.0644); Very rare (popmax 0.00187%, nfe).

How common is ADCK2 p.Pro85Ala (c.253C>G) in the general population?

ADCK2 p.Pro85Ala (c.253C>G) is very rare (popmax 0.00187%, nfe) (gnomAD).

What do computational predictors say about ADCK2 p.Pro85Ala (c.253C>G)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

ADCK2 p.Pro85Ala

c.253C>G · VCV4011536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -6.53	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 -2.1	GERP -2.8
Regional constraint	o/e 0.87	unconstrained · MANE · 21 kb · p 0.00024 · regional, not allelic
Overall
CADD	0.015	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

Grpmax group 0.00187% European (non-Finnish) · 22/1,179,074 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00143% 23/1,604,986 alleles · very rare exomes 22/1,452,870 · genomes 1/152,116 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00187%	53,594
Finnishnot grpmax-eligible	0.00176%	56,724

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: ADCK2
Protein: p.Pro85Ala
Coding: c.253C>G
MANE Select: NM_052853
Type: single nucleotide variant
Location: chr7:140673583 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.45

Full ADCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADCK2 p.Ala217Pro Uncertain significance ★ ⚠ same type
ADCK2 p.Ala293Gly Uncertain significance ★ ⚠ same type
ADCK2 p.Ala293Val Uncertain significance ★ ⚠ same type
ADCK2 p.Ala319Thr Uncertain significance ★ ⚠ same type
ADCK2 p.Ala465Val Uncertain significance ★ ⚠ same type
ADCK2 p.Ala510Thr Uncertain significance ★ ⚠ same type
ADCK2 p.Ala78Ser Uncertain significance ★ ⚠ same type
ADCK2 p.Arg292Trp 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/adck2-p-pro85ala (accessed [today's date]).

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