Is DPH6 p.Arg241His (c.722G>A) pathogenic?

DPH6 p.Arg241His (c.722G>A) is classified Uncertain significance in DPH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: likely benign (0.0879); Very rare (popmax 0.00875%, nfe).

How common is DPH6 p.Arg241His (c.722G>A) in the general population?

DPH6 p.Arg241His (c.722G>A) is very rare (popmax 0.00875%, nfe) (gnomAD).

What do computational predictors say about DPH6 p.Arg241His (c.722G>A)?

AlphaMissense predicts likely benign (score 0.0879) — an in-silico prediction, not a clinical call.

DPH6 p.Arg241His

c.722G>A · VCV3842229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00875%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0879	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -10.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.48, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 174 kb · p 0.78 · regional, not allelic
Overall
CADD	22.5	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 0.00875% European (non-Finnish) · 103/1,176,770 alleles

Filtering AF 0.00734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00686%

Overall 0.00709% 114/1,607,200 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00875%	11,425
Admixed American	0.00679%	14,721
Remaining individualsnot grpmax-eligible	0.00322%	31,095
African / African-American	0.00268%	37,252
East Asian	0.00224%	44,548
South Asian	0.00222%	45,015

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.Arg241His
Coding: c.722G>A
MANE Select: NM_080650
Type: single nucleotide variant
Location: chr15:35373549 (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.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
DPH6 p.Cys199Phe 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-arg241his (accessed [today's date]).

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