Is RFC4 p.Asp137= (c.411T>C) pathogenic?

RFC4 p.Asp137= (c.411T>C) is classified Likely benign in RFC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). Absent from gnomAD v4.1.

How common is RFC4 p.Asp137= (c.411T>C) in the general population?

RFC4 p.Asp137= (c.411T>C) is absent from gnomAD v4.1 (gnomAD).

RFC4 p.Asp137=

c.411T>C · VCV4153045

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2.6	GERP 0.7, phastCons 1
Overall
CADD	11.75	PHRED · no single calibrated threshold — expert panels disagree

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: RFC4
Protein: p.Asp137=
Coding: c.411T>C
MANE Select: NM_002916
Type: single nucleotide variant
Location: chr3:186792947 (GRCh38)
Gene constraint: LOEUF 1.096 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.68 · 16 PDB

Full RFC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RFC4 c.996+9G>A Benign ★★ same type
RFC4 c.290+5G>T Likely pathogenic ★ same type
RFC4 p.Ala271Val Uncertain significance ★ ⚠ same type
RFC4 p.Ala279Pro Uncertain significance ★ ⚠ same type
RFC4 p.Ala279Thr Uncertain significance ★ ⚠ same type
RFC4 p.Ala339Glu Uncertain significance ★ ⚠ same type
RFC4 p.Ala339Val Uncertain significance ★ ⚠ same type
RFC4 p.Ala342Val 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/rfc4-p-asp137 (accessed [today's date]).

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