Is RAD1 p.Pro102Ser (c.304C>T) pathogenic?

RAD1 p.Pro102Ser (c.304C>T) is classified Uncertain significance in RAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.0952); Ultra-rare (popmax 0.018%, eas).

How common is RAD1 p.Pro102Ser (c.304C>T) in the general population?

RAD1 p.Pro102Ser (c.304C>T) is ultra-rare (popmax 0.018%, eas) (gnomAD).

What do computational predictors say about RAD1 p.Pro102Ser (c.304C>T)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

RAD1 p.Pro102Ser

c.304C>T · VCV4149646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -8.69	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 8.6	GERP 1.1, phastCons 1
Overall
CADD	20.2	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 0.018% East Asian · 8/44,440 alleles

Filtering AF 0.00891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00646%

Overall 0.000649% 10/1,541,702 alleles · ultra-rare exomes 6/1,389,494 · genomes 4/152,208 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.018%	5,555
Admixed American	0.00186%	53,660
African / African-American	0.00138%	72,450

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: RAD1
Protein: p.Pro102Ser
Coding: c.304C>T
MANE Select: NM_002853
Type: single nucleotide variant
Location: chr5:34913473 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.56 · 7 PDB

Full RAD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAD1 p.Ala196Thr Uncertain significance ★ ⚠ same type
RAD1 p.Ala40Thr Uncertain significance ★ ⚠ same type
RAD1 p.Ala63Thr Uncertain significance ★ ⚠ same type
RAD1 p.Arg109Gln Uncertain significance ★ ⚠ same type
RAD1 p.Arg109Pro Uncertain significance ★ ⚠ same type
RAD1 p.Arg109Ter Uncertain significance ★ same type
RAD1 p.Arg164Cys Uncertain significance ★ ⚠ same type
RAD1 p.Arg164His 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/rad1-p-pro102ser (accessed [today's date]).

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