Is DCBLD2 p.Lys391= (c.1173A>G) pathogenic?

DCBLD2 p.Lys391= (c.1173A>G) is classified Benign in DCBLD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-10-19). Common (popmax 5.09%, afr) — too common for a highly-penetrant pathogenic allele.

DCBLD2 p.Lys391=

Q: How common is DCBLD2 p.Lys391= (c.1173A>G) in the general population?

DCBLD2 p.Lys391= (c.1173A>G) is common (popmax 5.09%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1173A>G · rs116350450 · VCV787020

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.09%, 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.
REVEL	0.075	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.95	GERP -4.5, phastCons 0.001
Overall
CADD	6.489	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.09% African / African-American · 3,819/75,038 alleles

Filtering AF 4.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.9%

Overall 0.261% 4,205/1,613,730 alleles · common exomes 2,005/1,461,406 · genomes 2,200/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.09%	20
Remaining individualsnot grpmax-eligible	0.258%	388
Admixed American	0.247%	405
Middle Eastern	0.165%	606
South Asian	0.00878%	11,386
European (non-Finnish)	0.005%	19,995

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: DCBLD2
Protein: p.Lys391=
Coding: c.1173A>G
MANE Select: NM_080927
dbSNP: rs116350450
Type: single nucleotide variant
Location: chr3:98817808 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.13
Residue 391: the f5/8 type c domain

Full DCBLD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCBLD2 p.Ala182Thr Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala24Ser Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala304Glu Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala304Thr Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala304Val Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala341Thr Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala482Asp Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala5Ser 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/dcbld2-p-lys391 (accessed [today's date]).

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