Is DPH1 p.Asn52Ser (c.155A>G) pathogenic?

DPH1 p.Asn52Ser (c.155A>G) is classified Uncertain significance in DPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-20). AlphaMissense: likely benign (0.1263); Very rare (popmax 0.00446%, eas); Associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 1.

How common is DPH1 p.Asn52Ser (c.155A>G) in the general population?

DPH1 p.Asn52Ser (c.155A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DPH1 p.Asn52Ser (c.155A>G)?

AlphaMissense predicts likely benign (score 0.1263) — an in-silico prediction, not a clinical call.

DPH1 p.Asn52Ser

Q: What condition is associated with DPH1 p.Asn52Ser (c.155A>G)?

DPH1 p.Asn52Ser (c.155A>G) is associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 1 (ClinVar).

c.155A>G · rs140382122 · VCV2442231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

developmental delay with short stature, dysmorphic facial features, and sparse hair 1

Computational evidence

Protein change
AlphaMissense	0.1263	likely benign
REVEL	0.327	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 12 kb · p 0.074 · 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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM N57S vs ClinVar N52S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000372% 6/1,614,190 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,442
Admixed American	0.00333%	30,014
Remaining individualsnot grpmax-eligible	0.0016%	62,506
South Asian	0.0011%	91,078

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.Asn52Ser
Coding: c.155A>G
MANE Select: NM_001383
dbSNP: rs140382122
Type: single nucleotide variant
Location: chr17:2033598 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.00

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

Disease context

developmental delay with short stature, dysmorphic facial features, and sparse hair 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPH1 p.Leu229Pro Pathogenic/Likely pathogenic ★★ same condition
DPH1 p.Arg144Trp Uncertain significance ★★ ⚠ same condition
DPH1 p.Arg22Gln Uncertain significance ★★ ⚠ same condition
DPH1 p.Arg47Trp Uncertain significance ★★ ⚠ same condition
DPH1 p.Asp231Glu Uncertain significance ★★ ⚠ same condition
DPH1 p.Gln269His Uncertain significance ★★ ⚠ same condition
DPH1 c.400+1G>A Likely pathogenic ★ same condition
DPH1 p.Arg218Ter Likely pathogenic ★ 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-asn52ser (accessed [today's date]).

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