Is SMAD2 p.Ser82Pro (c.244T>C) pathogenic?

SMAD2 p.Ser82Pro (c.244T>C) is classified Uncertain significance in SMAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-04). AlphaMissense: likely benign (0.1221); Absent from gnomAD v4.1.

How common is SMAD2 p.Ser82Pro (c.244T>C) in the general population?

SMAD2 p.Ser82Pro (c.244T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMAD2 p.Ser82Pro (c.244T>C)?

AlphaMissense predicts likely benign (score 0.1221) — an in-silico prediction, not a clinical call.

SMAD2 p.Ser82Pro

c.244T>C · rs2511354421 · VCV2750195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1221 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1221	likely benign
REVEL	0.647	pathogenic-leaning
SaProt	LLR -7.07	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 27 kb · p 4e-05 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SMAD2
Protein: p.Ser82Pro
Coding: c.244T>C
MANE Select: NM_005901
dbSNP: rs2511354421
Type: single nucleotide variant
Location: chr18:47870557 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.50 · 10 PDB
Residue 82: the mh1 domain

Full SMAD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMAD2 c.237-2A>G Likely pathogenic ★★ same type
SMAD2 p.Arg120Ter Pathogenic/Likely pathogenic ★★ same type
SMAD2 p.Arg182Ter Pathogenic ★★ same type
SMAD2 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same type
SMAD2 p.Gln264Ter Pathogenic/Likely pathogenic ★★ same type
SMAD2 p.Tyr406Cys Pathogenic/Likely pathogenic ★★ same type
SMAD2 c.520+4G>A Uncertain significance ★★ same type
SMAD2 c.997+5G>A 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/smad2-p-ser82pro (accessed [today's date]).

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