Is DLGAP2 p.Arg214Lys (c.641G>A) pathogenic?

DLGAP2 p.Arg214Lys (c.641G>A) is classified Benign in DLGAP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-03-01). AlphaMissense: likely benign (0.1145); Rare (popmax 0.48%, mid).

How common is DLGAP2 p.Arg214Lys (c.641G>A) in the general population?

DLGAP2 p.Arg214Lys (c.641G>A) is rare (popmax 0.48%, mid) (gnomAD).

What do computational predictors say about DLGAP2 p.Arg214Lys (c.641G>A)?

AlphaMissense predicts likely benign (score 0.1145) — an in-silico prediction, not a clinical call.

DLGAP2 p.Arg214Lys

c.641G>A · rs200052111 · VCV3050378

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1145 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.48%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1145	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 8.3, phastCons 1
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R213K vs ClinVar R214K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.48% Middle Eastern · 29/6,036 alleles

Filtering AF 0.344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.297%

Overall 0.235% 3,726/1,583,196 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.34%	75
Amishnot grpmax-eligible	0.877%	114
Middle Easterngrpmax	0.48%	208
Finnishnot grpmax-eligible	0.306%	327
Remaining individualsnot grpmax-eligible	0.281%	356
European (non-Finnish)	0.236%	424
Admixed American	0.12%	830
South Asian	0.106%	944
African / African-American	0.0456%	2,191
East Asian	0.00231%	43,268

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: DLGAP2
Protein: p.Arg214Lys
Coding: c.641G>A
MANE Select: NM_001346810
dbSNP: rs200052111
Type: single nucleotide variant
Location: chr8:1549094 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 48.83

Full DLGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLGAP2 c.1810+14A>G Benign ★★ same type
DLGAP2 c.2160+19C>G Benign ★★ same type
DLGAP2 p.Glu678= Benign ★★ same type
DLGAP2 p.Pro464Gln Benign ★★ same type
DLGAP2 c.2203-7G>T Uncertain significance ★ same type
DLGAP2 p.Ala1019Gly Uncertain significance ★ ⚠ same type
DLGAP2 p.Ala1026Val Uncertain significance ★ ⚠ same type
DLGAP2 p.Ala116Thr 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/dlgap2-p-arg214lys (accessed [today's date]).

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