Is CRLF1 p.Arg340= (c.1020C>A) pathogenic?

CRLF1 p.Arg340= (c.1020C>A) is classified Likely benign in CRLF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-10). Absent from gnomAD v4.1.

How common is CRLF1 p.Arg340= (c.1020C>A) in the general population?

CRLF1 p.Arg340= (c.1020C>A) is absent from gnomAD v4.1 (gnomAD).

CRLF1 p.Arg340=

c.1020C>A · rs35459448 · VCV2024156

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 0.062	GERP -3, phastCons 0.86
Overall
CADD	6.309	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: CRLF1
Protein: p.Arg340=
Coding: c.1020C>A
MANE Select: NM_004750
dbSNP: rs35459448
Type: single nucleotide variant
Location: chr19:18596626 (GRCh38)
Gene constraint: LOEUF 1.045 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.15 · 1 PDB
Residue 340: a UniProt-annotated variant site (in ciss1); the fibronectin type-iii 2 domain; the 'disordered' region

Full CRLF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRLF1 p.Arg340Cys Uncertain significance ★ same residue
CRLF1 p.Arg340Gly Uncertain significance ★ ⚠ same residue
CRLF1 p.Arg340His Uncertain significance ★ ⚠ same residue
CRLF1 c.397+1G>A Pathogenic/Likely pathogenic ★★ same type
CRLF1 p.Trp177Ter Pathogenic ★★ same type
CRLF1 p.Arg119Cys Uncertain significance ★★ ⚠ same type
CRLF1 p.Arg81His Uncertain significance ★★ ⚠ same type
CRLF1 p.Asn168Lys 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/crlf1-p-arg340 (accessed [today's date]).

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