Is DPH7 p.His253Arg (c.758A>G) pathogenic?

DPH7 p.His253Arg (c.758A>G) is classified Uncertain significance in DPH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). AlphaMissense: likely benign (0.2473); Very rare (popmax 0.00452%, nfe).

How common is DPH7 p.His253Arg (c.758A>G) in the general population?

DPH7 p.His253Arg (c.758A>G) is very rare (popmax 0.00452%, nfe) (gnomAD).

What do computational predictors say about DPH7 p.His253Arg (c.758A>G)?

AlphaMissense predicts likely benign (score 0.2473) — an in-silico prediction, not a clinical call.

DPH7 p.His253Arg

c.758A>G · rs771871783 · VCV2215841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2473 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00452%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2473	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -13.19	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 1.4	GERP 0.65, phastCons 0.004
Regional constraint	o/e 1.09	unconstrained · MANE · 24 kb · p 0.032 · regional, not allelic
Overall
CADD	20.7	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 0.00452% European (non-Finnish) · 53/1,171,654 alleles

Filtering AF 0.00353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0032%

Overall 0.00338% 54/1,596,548 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00452%	22,107
Remaining individualsnot grpmax-eligible	0.00162%	61,766

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: DPH7
Protein: p.His253Arg
Coding: c.758A>G
MANE Select: NM_138778
dbSNP: rs771871783
Type: single nucleotide variant
Location: chr9:137564911 (GRCh38)
Gene constraint: LOEUF 1.37 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.62

Full DPH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH7 p.Ala105Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala16Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala193Val Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Pro Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Val Uncertain significance ★ ⚠ same type
DPH7 p.Ala427Thr Uncertain significance ★ ⚠ same type
DPH7 p.Arg237Ser 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/dph7-p-his253arg (accessed [today's date]).

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