Is DPH6 p.Gly24Arg (c.70G>A) pathogenic?

DPH6 p.Gly24Arg (c.70G>A) is classified Uncertain significance in DPH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: likely pathogenic (0.7309); Very rare (popmax 0.00026%, nfe).

How common is DPH6 p.Gly24Arg (c.70G>A) in the general population?

DPH6 p.Gly24Arg (c.70G>A) is very rare (popmax 0.00026%, nfe) (gnomAD).

What do computational predictors say about DPH6 p.Gly24Arg (c.70G>A)?

AlphaMissense predicts likely pathogenic (score 0.7309) — an in-silico prediction, not a clinical call.

DPH6 p.Gly24Arg

c.70G>A · VCV3842233

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7309 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00026%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7309	likely pathogenic
REVEL	0.611	indeterminate
SaProt	LLR -11.45	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 174 kb · p 0.78 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00026% European (non-Finnish) · 3/1,154,264 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00021% 3/1,428,962 alleles · very rare

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: DPH6
Protein: p.Gly24Arg
Coding: c.70G>A
MANE Select: NM_080650
Type: single nucleotide variant
Location: chr15:35542461 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.85

Full DPH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH6 p.Gly41Glu Benign ★★ same type
DPH6 p.Ala5Ser Uncertain significance ★ ⚠ same type
DPH6 p.Arg123His Uncertain significance ★ ⚠ same type
DPH6 p.Arg241His Uncertain significance ★ ⚠ same type
DPH6 p.Arg2Trp Uncertain significance ★ ⚠ same type
DPH6 p.Asp173Ala Uncertain significance ★ ⚠ same type
DPH6 p.Asp173His Uncertain significance ★ ⚠ same type
DPH6 p.Asp46Asn 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/dph6-p-gly24arg (accessed [today's date]).

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