Is CDKN1A p.Ser31Arg (c.93C>A) pathogenic?

CDKN1A p.Ser31Arg (c.93C>A) is classified Likely benign in CDKN1A (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-27). AlphaMissense: likely benign (0.0846); Common (popmax 48.1%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CDKN1A p.Ser31Arg (c.93C>A)?

AlphaMissense predicts likely benign (score 0.0846) — an in-silico prediction, not a clinical call.

CDKN1A p.Ser31Arg

Q: How common is CDKN1A p.Ser31Arg (c.93C>A) in the general population?

CDKN1A p.Ser31Arg (c.93C>A) is common (popmax 48.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.93C>A · rs1801270 · VCV17565

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0846 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 48.1%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0846	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -2.42	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 -0.98	GERP -3.7
Regional constraint	o/e 0.88	unconstrained · MANE · 1,695 bp · p 0.06 · regional, not allelic
Overall
CADD	2.378	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 48.1% East Asian · 21,576/44,844 alleles

Filtering AF 47.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.4%

Overall 9.89% 159,422/1,611,622 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	48.1%	2
Admixed American	30.5%	3
African / African-American	25.2%	4
Amishnot grpmax-eligible	13.6%	7
Middle Eastern	12.5%	8
Remaining individualsnot grpmax-eligible	11.3%	9
South Asian	10.5%	10
Ashkenazi Jewishnot grpmax-eligible	8.97%	11
European (non-Finnish)	6.53%	15
Finnishnot grpmax-eligible	5.65%	18

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.Ser31Arg
Coding: c.93C>A
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.Ser31= 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-ser31arg (accessed [today's date]).

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