Is DLGAP5 p.Ile85Val (c.253A>G) pathogenic?

DLGAP5 p.Ile85Val (c.253A>G) is classified Likely benign in DLGAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.057); Ultra-rare (popmax 0.0169%, mid).

How common is DLGAP5 p.Ile85Val (c.253A>G) in the general population?

DLGAP5 p.Ile85Val (c.253A>G) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

What do computational predictors say about DLGAP5 p.Ile85Val (c.253A>G)?

AlphaMissense predicts likely benign (score 0.057) — an in-silico prediction, not a clinical call.

DLGAP5 p.Ile85Val

c.253A>G · VCV3840367

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.057	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -4.07	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 -2.8	GERP -4.1
Regional constraint	o/e 1.05	unconstrained · MANE · 41 kb · p 0.094 · regional, not allelic
Overall
CADD	0.015	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 0.0169% Middle Eastern · 1/5,900 alleles

Filtering AF 0.0019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.00251% 40/1,593,736 alleles · ultra-rare exomes 35/1,441,500 · genomes 5/152,236 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,900
Remaining individualsnot grpmax-eligible	0.0065%	15,389
African / African-American	0.00407%	24,586
European (non-Finnish)	0.00265%	37,800
South Asian	0.00114%	87,394

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: DLGAP5
Protein: p.Ile85Val
Coding: c.253A>G
MANE Select: NM_014750
Type: single nucleotide variant
Location: chr14:55183739 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.52 · 4 PDB

Full DLGAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG1 p.His120Arg Uncertain significance ★★ ⚠ same type
DLG1 p.Ala262= Benign ★★ same type
DLG1 p.Asp633Glu Benign ★★ same type
DLG1 p.Ser470= Benign ★★ same type
DLG1 p.Val167= Benign ★★ same type
DLGAP5 c.1049+7A>C Benign ★★ same type
DLGAP5 c.2064-1G>A Likely pathogenic ★ same type
DLG1 c.484-11849C>T 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/dlgap5-p-ile85val (accessed [today's date]).

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