Is DLC1 p.Arg1247= (c.3741G>A) pathogenic?

DLC1 p.Arg1247= (c.3741G>A) is classified Uncertain significance in DLC1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-03-12). Rare (popmax 0.123%, afr).

How common is DLC1 p.Arg1247= (c.3741G>A) in the general population?

DLC1 p.Arg1247= (c.3741G>A) is rare (popmax 0.123%, afr) (gnomAD).

DLC1 p.Arg1247=

c.3741G>A · rs149560610 · VCV3032483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.123%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.52	GERP 0.66, phastCons 1
Overall
CADD	16.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% African / African-American · 92/74,860 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.095%

Overall 0.00663% 107/1,613,030 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.123%	814
South Asian	0.011%	9,102
Remaining individualsnot grpmax-eligible	0.0048%	20,825
Admixed American	0.00167%	59,946
European (non-Finnish)	8.48e-05%	1,179,344

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: DLC1
Protein: p.Arg1247=
Coding: c.3741G>A
MANE Select: NM_003746 · reported on NM_182643
dbSNP: rs149560610
Type: single nucleotide variant
Location: chr8:13091432 (GRCh38)
Structure: AlphaFold pLDDT 95.45 · 22 PDB

Full DLC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLC1 c.2991-5C>A Uncertain significance ★★ same type
DLC1 p.Ala1268Val Uncertain significance ★★ ⚠ same type
DLC1 p.Ala1278Thr Uncertain significance ★★ ⚠ same type
DLC1 p.Ala167Pro Uncertain significance ★★ ⚠ same type
DLC1 p.Ala350Val Uncertain significance ★★ ⚠ same type
DLC1 p.Ala752Gly Uncertain significance ★★ ⚠ same type
DLC1 p.Ala821Thr Uncertain significance ★★ ⚠ same type
DLC1 p.Ala821Val 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/dlc1-p-arg1247 (accessed [today's date]).

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