Is ADCK2 p.Leu42Phe (c.124C>T) pathogenic?

ADCK2 p.Leu42Phe (c.124C>T) is classified Likely benign in ADCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: likely benign (0.1052); Rare (popmax 0.648%, nfe).

How common is ADCK2 p.Leu42Phe (c.124C>T) in the general population?

ADCK2 p.Leu42Phe (c.124C>T) is rare (popmax 0.648%, nfe) (gnomAD).

What do computational predictors say about ADCK2 p.Leu42Phe (c.124C>T)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

ADCK2 p.Leu42Phe

c.124C>T · rs140971515 · VCV2658020

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.648%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -7.58	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 2.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 21 kb · p 0.00024 · regional, not allelic
Overall
CADD	16.6	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 0.648% European (non-Finnish) · 7,638/1,178,140 alleles

Filtering AF 0.636% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.631%

Overall 0.535% 8,602/1,608,808 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.648%	154
Remaining individualsnot grpmax-eligible	0.511%	196
Middle Eastern	0.381%	262
South Asian	0.262%	382
Admixed American	0.227%	441
Finnishnot grpmax-eligible	0.167%	599
Ashkenazi Jewishnot grpmax-eligible	0.159%	627
African / African-American	0.131%	765
Amishnot grpmax-eligible	0.11%	910
East Asian	0.00224%	44,704

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.Leu42Phe
Coding: c.124C>T
MANE Select: NM_052853
dbSNP: rs140971515
Type: single nucleotide variant
Location: chr7:140673454 (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.Leu42His Uncertain significance ★ ⚠ same residue
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

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-leu42phe (accessed [today's date]).

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