Is ODAPH p.Arg77Ter (c.229C>T) pathogenic?

ODAPH p.Arg77Ter (c.229C>T) is classified Pathogenic in ODAPH (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-17). Very rare (popmax 0.0022%, sas); Associated with amelogenesis imperfecta hypomaturation type 2A4.

What condition is associated with ODAPH p.Arg77Ter (c.229C>T)?

ODAPH p.Arg77Ter (c.229C>T) is associated with amelogenesis imperfecta hypomaturation type 2A4 (ClinVar).

How common is ODAPH p.Arg77Ter (c.229C>T) in the general population?

ODAPH p.Arg77Ter (c.229C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

ODAPH p.Arg77Ter

c.229C>T · rs866941536 · VCV37216

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

amelogenesis imperfecta hypomaturation type 2A4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.39	GERP -3.1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,614,164 alleles · very rare exomes 10/1,461,894 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000593%	168,576

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.Arg77Ter
Coding: c.229C>T
MANE Select: NM_178497
dbSNP: rs866941536
Type: single nucleotide variant
Location: chr4:75564275 (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

amelogenesis imperfecta hypomaturation type 2A4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C4orf26 c.318G>A Likely pathogenic ★ same condition
ODAPH c.68-2A>T Pathogenic same condition
ODAPH p.Cys43Ter Pathogenic same condition
ODAPH p.Pro76fs Likely pathogenic ★ same condition
ODAPH p.Val18fs Likely pathogenic ★ same condition
ODAPH c.67+138A>G Benign ★★ same type
ODAPH c.67+269A>C Benign ★★ same type
ODAPH p.Arg109His 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-arg77ter (accessed [today's date]).

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