Is DLGAP3 p.Ser406= (c.1218C>T) pathogenic?

DLGAP3 p.Ser406= (c.1218C>T) is classified Benign/Likely benign in DLGAP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-01). Ultra-rare (popmax 0.03%, amr).

How common is DLGAP3 p.Ser406= (c.1218C>T) in the general population?

DLGAP3 p.Ser406= (c.1218C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

DLGAP3 p.Ser406=

c.1218C>T · rs150566254 · VCV724007

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

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 -7.6	GERP -5.7
Overall
CADD	3.797	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/60,020 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0191%

Overall 0.0774% 1,249/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.81%	36
Remaining individualsnot grpmax-eligible	0.202%	496
Admixed Americangrpmax	0.03%	3,334
European (non-Finnish)	0.0222%	4,504
African / African-American	0.00666%	15,010
East Asian	0.00446%	22,434
South Asian	0.00329%	30,359

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DLGAP3
Protein: p.Ser406=
Coding: c.1218C>T
MANE Select: NM_001080418
dbSNP: rs150566254
Type: single nucleotide variant
Location: chr1:34900163 (GRCh38)
Gene constraint: LOEUF 0.367 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.83
Residue 406: a modified residue (phosphoserine); the 'disordered' region

Full DLGAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLGAP3 p.Arg793= Benign ★★ same type
DLGAP3 p.Gly306= Benign ★★ same type
DLGAP3 p.Pro764= Benign ★★ same type
DLGAP3 p.Thr334= Benign ★★ same type
DLGAP3 p.Lys889Arg Uncertain significance ★ ⚠ same type
DLGAP3 p.Ala347= Likely benign ★ same type
DLGAP3 p.Arg627= Benign ★ same type
DLGAP3 p.Pro45His Likely benign ★ 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/dlgap3-p-ser406 (accessed [today's date]).

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