Is ODAPH p.Val18= (c.54A>T) pathogenic?

ODAPH p.Val18= (c.54A>T) is classified Likely benign in ODAPH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-18). Ultra-rare (popmax 0.0253%, nfe); Associated with ODAPH-related disorder.

What condition is associated with ODAPH p.Val18= (c.54A>T)?

ODAPH p.Val18= (c.54A>T) is associated with ODAPH-related disorder (ClinVar).

How common is ODAPH p.Val18= (c.54A>T) in the general population?

ODAPH p.Val18= (c.54A>T) is ultra-rare (popmax 0.0253%, nfe) (gnomAD).

ODAPH p.Val18=

c.54A>T · rs754990168 · VCV3041580

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, nfe)

Conditions

ODAPH-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.057	GERP -5
Overall
CADD	4.489	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% European (non-Finnish) · 298/1,179,992 alleles

Filtering AF 0.0229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.0204% 330/1,614,036 alleles · ultra-rare exomes 312/1,461,836 · genomes 18/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0253%	3,960
Finnishnot grpmax-eligible	0.025%	4,003
Remaining individualsnot grpmax-eligible	0.0096%	10,415
Admixed American	0.00833%	12,002
African / African-American	0.00667%	14,984

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: ODAPH
Protein: p.Val18=
Coding: c.54A>T
MANE Select: NM_178497
dbSNP: rs754990168
Type: single nucleotide variant
Location: chr4:75556136 (GRCh38)
Gene constraint: LOEUF 1.704 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 61.64

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

Disease context

ODAPH-related disorder

Similar variants

ODAPH p.Val18fs Likely pathogenic ★ same residue
C4orf26 c.318G>A Likely pathogenic ★ same condition
ODAPH c.68-2A>G Likely pathogenic same condition
ODAPH c.67+445T>G Likely benign same condition
ODAPH c.*73C>T Likely benign same condition
ODAPH p.Ala40Ser Likely benign same condition
ODAPH c.67+138A>G Benign ★★ same type
ODAPH c.67+269A>C Benign ★★ 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/odaph-p-val18 (accessed [today's date]).

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