Is DPH3 p.Lys36Arg (c.107A>G) pathogenic?

DPH3 p.Lys36Arg (c.107A>G) is classified Uncertain significance in DPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0822); Ultra-rare (popmax 0.066%, mid).

How common is DPH3 p.Lys36Arg (c.107A>G) in the general population?

DPH3 p.Lys36Arg (c.107A>G) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about DPH3 p.Lys36Arg (c.107A>G)?

AlphaMissense predicts likely benign (score 0.0822) — an in-silico prediction, not a clinical call.

DPH3 p.Lys36Arg

c.107A>G · VCV4244419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0822 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0822	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.3	GERP -0.34, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,109 bp · p 0.77 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,060 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00452% 73/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,515
Remaining individualsnot grpmax-eligible	0.0064%	15,624
European (non-Finnish)	0.00525%	19,031
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
East Asian	0.00223%	44,868
Finnishnot grpmax-eligible	0.00156%	64,028

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: DPH3
Protein: p.Lys36Arg
Coding: c.107A>G
MANE Select: NM_206831
Type: single nucleotide variant
Location: chr3:16264770 (GRCh38)
Gene constraint: LOEUF 1.439 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.51 · 1 PDB
Residue 36: the dph-type mb domain; an α-helix

Full DPH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH3 p.Asp12Ala Uncertain significance ★ ⚠ same type
DPH3 p.Asp18Gly Uncertain significance ★ ⚠ same type
DPH3 p.Asp62Asn Uncertain significance ★ ⚠ same type
DPH3 p.Cys28Arg Uncertain significance ★ ⚠ same type
DPH3 p.Cys51Ser Uncertain significance ★ ⚠ same type
DPH3 p.Pro25Leu Uncertain significance ★ ⚠ same type
DPH3 p.Thr21Ser Uncertain significance ★ ⚠ same type
DPH3 p.Thr47Lys 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/dph3-p-lys36arg (accessed [today's date]).

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