Is DLC1 p.Ser1167= (c.3501G>A) pathogenic?

DLC1 p.Ser1167= (c.3501G>A) is classified Benign in DLC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 24.1%, afr) — too common for a highly-penetrant pathogenic allele.

DLC1 p.Ser1167=

Q: How common is DLC1 p.Ser1167= (c.3501G>A) in the general population?

DLC1 p.Ser1167= (c.3501G>A) is common (popmax 24.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3501G>A · rs658856 · VCV1179905

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 24.1%, afr) — too common for a highly-penetrant pathogenic allele

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 -15	GERP -3.7
Overall
CADD	0.487	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.1% African / African-American · 18,021/74,928 alleles

Filtering AF 23.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.6%

Overall 6.08% 98,066/1,613,980 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	24.1%	4
South Asian	9.59%	10
Middle Eastern	9.49%	11
Ashkenazi Jewishnot grpmax-eligible	8.63%	12
Remaining individualsnot grpmax-eligible	6.74%	15
Finnishnot grpmax-eligible	6.71%	15
Admixed American	5.04%	20
European (non-Finnish)	4.66%	21
Amishnot grpmax-eligible	4.07%	25
East Asian	3.71%	27

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.Ser1167=
Coding: c.3501G>A
MANE Select: NM_003746 · reported on NM_182643
dbSNP: rs658856
Type: single nucleotide variant
Location: chr8:13094784 (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 p.Ser1167Leu Uncertain significance ★ ⚠ same residue
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

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-ser1167 (accessed [today's date]).

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