Is DLGAP3 p.Pro45His (c.134C>A) pathogenic?

DLGAP3 p.Pro45His (c.134C>A) is classified Likely benign in DLGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-17). AlphaMissense: likely benign (0.1138); Rare (popmax 0.313%, eas).

How common is DLGAP3 p.Pro45His (c.134C>A) in the general population?

DLGAP3 p.Pro45His (c.134C>A) is rare (popmax 0.313%, eas) (gnomAD).

What do computational predictors say about DLGAP3 p.Pro45His (c.134C>A)?

AlphaMissense predicts likely benign (score 0.1138) — an in-silico prediction, not a clinical call.

DLGAP3 p.Pro45His

c.134C>A · rs552097335 · VCV722225

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1138 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.313%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1138	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -9.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 370 bp · p 0.7 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.313% East Asian · 138/44,122 alleles

Filtering AF 0.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.254%

Overall 0.0117% 186/1,593,864 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.313%	320
Remaining individualsnot grpmax-eligible	0.0681%	1,469
Admixed American	0.00526%	19,011
South Asian	0.00114%	87,446
European (non-Finnish)	0.000171%	585,350

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.Pro45His
Coding: c.134C>A
MANE Select: NM_001080418
dbSNP: rs552097335
Type: single nucleotide variant
Location: chr1:34905250 (GRCh38)
Gene constraint: LOEUF 0.367 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.83

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

Similar variants

DLGAP3 p.Pro45Thr Likely benign ★ same residue
DLGAP3 p.Arg793= Benign ★★ same type
DLGAP3 p.Gly306= Benign ★★ same type
DLGAP3 p.Pro764= Benign ★★ same type
DLGAP3 p.Ser406= Benign/Likely benign ★★ same type
DLGAP3 p.Thr334= Benign ★★ same type
DLGAP3 p.Lys889Arg Uncertain significance ★ ⚠ same type
DLGAP3 p.Ala347= 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-pro45his (accessed [today's date]).

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