Is PROK2 p.Ala24Val (c.71C>T) pathogenic?

PROK2 p.Ala24Val (c.71C>T) is classified Likely benign in PROK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely benign (0.09); No allele count reported in gnomAD v4.1 (AN 1,250,028); Associated with Inborn genetic diseases.

What condition is associated with PROK2 p.Ala24Val (c.71C>T)?

PROK2 p.Ala24Val (c.71C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PROK2 p.Ala24Val (c.71C>T) in the general population?

PROK2 p.Ala24Val (c.71C>T) is no allele count reported in gnomAD v4.1 (AN 1,250,028) (gnomAD).

What do computational predictors say about PROK2 p.Ala24Val (c.71C>T)?

AlphaMissense predicts likely benign (score 0.09) — an in-silico prediction, not a clinical call.

PROK2 p.Ala24Val

c.71C>T · VCV3783515

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.09 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,250,028)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.09	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -7.90	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 5.5	GERP 0.92, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 12 kb · p 0.61 · regional, not allelic
Overall
CADD	11.48	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

No allele count reported in gnomAD v4.1 (AN 1,250,028). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PROK2
Protein: p.Ala24Val
Coding: c.71C>T
MANE Select: NM_001126128
Type: single nucleotide variant
Location: chr3:71784982 (GRCh38)
Gene constraint: LOEUF 1.052 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 69.22
Residue 24: a UniProt-annotated variant site (in hh4; phenotype consistent with kallmann syndrome)

Full PROK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PROK2 p.Ala24Pro Conflicting classifications of pathogenicity ⚠ same residue
PROK2 p.Ala24Ser Uncertain significance ⚠ same residue
PROK2 p.Arg122Gln Uncertain significance ★★ ⚠ same condition
PROK2 p.Asp66Asn Uncertain significance ★★ ⚠ same condition
PROK2 p.Val29Met Uncertain significance ★★ ⚠ same condition
PROK2 p.Ala33Pro Uncertain significance ★ ⚠ same condition
PROK2 p.Arg117Gln Uncertain significance ★ ⚠ same condition
PROK2 p.Asn76Ser Uncertain significance ★ ⚠ same condition

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/prok2-p-ala24val (accessed [today's date]).

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