Is CDKN2D p.Val102Met (c.304G>A) pathogenic?

CDKN2D p.Val102Met (c.304G>A) is classified Uncertain significance in CDKN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.1782); Ultra-rare (popmax 0.0117%, amr).

How common is CDKN2D p.Val102Met (c.304G>A) in the general population?

CDKN2D p.Val102Met (c.304G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about CDKN2D p.Val102Met (c.304G>A)?

AlphaMissense predicts likely benign (score 0.1782) — an in-silico prediction, not a clinical call.

CDKN2D p.Val102Met

c.304G>A · rs141595298 · VCV3141671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1782 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1782	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.84	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 -0.87	GERP -2.7
Regional constraint	o/e 0.85	unconstrained · MANE · 1,592 bp · p 0.022 · regional, not allelic
Overall
CADD	11.67	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 0.0117% Admixed American · 7/60,014 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00136% 22/1,614,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.008%	12,498
African / African-American	0.00534%	18,732
European (non-Finnish)	0.000508%	196,671

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: CDKN2D
Protein: p.Val102Met
Coding: c.304G>A
MANE Select: NM_001800
dbSNP: rs141595298
Type: single nucleotide variant
Location: chr19:10567255 (GRCh38)
Gene constraint: LOEUF 1.426 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 95.91 · 2 PDB

Full CDKN2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN2D p.Ala128Pro Uncertain significance ★ ⚠ same type
CDKN2D p.Ala137Pro Uncertain significance ★ ⚠ same type
CDKN2D p.Ala146Thr Uncertain significance ★ ⚠ same type
CDKN2D p.Ala57Thr Uncertain significance ★ ⚠ same type
CDKN2D p.Arg7Pro Uncertain significance ★ ⚠ same type
CDKN2D p.Arg83Cys Uncertain significance ★ ⚠ same type
CDKN2D p.Asp20Asn Uncertain significance ★ ⚠ same type
CDKN2D p.Gln152Pro 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/cdkn2d-p-val102met (accessed [today's date]).

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