Is CDKN1A p.Ser31= (c.93C>T) pathogenic?

CDKN1A p.Ser31= (c.93C>T) is classified Likely benign in CDKN1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-01). Ultra-rare (popmax 0.0822%, mid).

How common is CDKN1A p.Ser31= (c.93C>T) in the general population?

CDKN1A p.Ser31= (c.93C>T) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

CDKN1A p.Ser31=

c.93C>T · rs1801270 · VCV2656516

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.98	GERP -3.7
Overall
CADD	4.703	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0822% Middle Eastern · 5/6,084 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00614% 99/1,611,596 alleles · ultra-rare exomes 97/1,459,436 · genomes 2/152,160 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,217
European (non-Finnish)	0.00763%	13,111
Remaining individualsnot grpmax-eligible	0.0048%	20,825
African / African-American	0.00133%	74,910

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: CDKN1A
Protein: p.Ser31=
Coding: c.93C>T
MANE Select: NM_000389
dbSNP: rs1801270
Type: single nucleotide variant
Location: chr6:36684194 (GRCh38)
Gene constraint: LOEUF 1.492 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.16 · 13 PDB
Residue 31: a UniProt-annotated variant site (in); an α-helix

Full CDKN1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN1A p.Ser31Arg Likely benign ★ same residue
CDKN1A p.Arg84Gln Likely benign ★★ same type
CDKN1A p.Pro4= Benign/Likely benign ★★ same type
CDKN1A p.Thr80= Likely benign ★★ same type
CDKN1A p.Ala106Val Uncertain significance ★ ⚠ same type
CDKN1A p.Arg20His Uncertain significance ★ ⚠ same type
CDKN1A p.Arg32His Uncertain significance ★ ⚠ same type
CDKN1A p.Arg46His 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/cdkn1a-p-ser31 (accessed [today's date]).

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