Is DPH1 p.Ile46Val (c.136A>G) pathogenic?

DPH1 p.Ile46Val (c.136A>G) is classified Likely benign in DPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.066); Very rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with DPH1 p.Ile46Val (c.136A>G)?

DPH1 p.Ile46Val (c.136A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DPH1 p.Ile46Val (c.136A>G) in the general population?

DPH1 p.Ile46Val (c.136A>G) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DPH1 p.Ile46Val (c.136A>G)?

AlphaMissense predicts likely benign (score 0.066) — an in-silico prediction, not a clinical call.

DPH1 p.Ile46Val

c.136A>G · rs758225925 · VCV2256825

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.066 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.066	likely benign
REVEL	0.011	strongly benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.14, phastCons 0.94
Regional constraint	o/e 1.07	unconstrained · MANE · 12 kb · p 0.074 · regional, not allelic
Overall
CADD	3.655	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I51V vs ClinVar I46V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,008 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00124% 20/1,614,112 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,001
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,088
European (non-Finnish)	0.00102%	98,338

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: DPH1
Protein: p.Ile46Val
Coding: c.136A>G
MANE Select: NM_001383
dbSNP: rs758225925
Type: single nucleotide variant
Location: chr17:2033579 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.00
Residue 46: a UniProt-annotated variant site (in)

Full DPH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPH1 p.Arg144Trp Uncertain significance ★★ ⚠ same condition
DPH1 p.Ile241Phe Uncertain significance ★★ same condition
DPH1 p.Lys38Thr Likely benign ★★ same condition
DPH1 c.279-5C>T Uncertain significance ★ same condition
DPH1 c.558+4G>C Uncertain significance ★ same condition
DPH1 c.-12C>T Uncertain significance ★ ⚠ same condition
DPH1 c.-2T>A Uncertain significance ★ ⚠ same condition
DPH1 c.-6C>G Uncertain significance ★ ⚠ same condition

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/dph1-p-ile46val (accessed [today's date]).

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