Is DPH7 p.Arg65His (c.194G>A) pathogenic?

DPH7 p.Arg65His (c.194G>A) is classified Uncertain significance in DPH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-18). AlphaMissense: likely benign (0.2171); Ultra-rare (popmax 0.052%, afr).

How common is DPH7 p.Arg65His (c.194G>A) in the general population?

DPH7 p.Arg65His (c.194G>A) is ultra-rare (popmax 0.052%, afr) (gnomAD).

What do computational predictors say about DPH7 p.Arg65His (c.194G>A)?

AlphaMissense predicts likely benign (score 0.2171) — an in-silico prediction, not a clinical call.

DPH7 p.Arg65His

c.194G>A · VCV3273597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2171 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.052%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2171	likely benign
REVEL	0.277	benign-leaning
SaProt	LLR -14.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.20	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 5.8	GERP 1.3, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 24 kb · p 0.032 · regional, not allelic
Overall
CADD	24.8	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 0.052% African / African-American · 39/75,042 alleles

Filtering AF 0.039% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0345%

Overall 0.00781% 126/1,613,992 alleles · ultra-rare exomes 93/1,461,702 · genomes 33/152,290 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0777%	1,287
African / African-Americangrpmax	0.052%	1,924
Admixed American	0.0233%	4,287
South Asian	0.0209%	4,793
Remaining individualsnot grpmax-eligible	0.0112%	8,929
East Asian	0.00446%	22,444
European (non-Finnish)	0.00186%	53,635

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg65His
Coding: c.194G>A
MANE Select: NM_138778
Type: single nucleotide variant
Location: chr9:137577563 (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-arg65his (accessed [today's date]).

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