Is ODAPH p.Ser93Pro (c.277T>C) pathogenic?

ODAPH p.Ser93Pro (c.277T>C) is classified Benign in ODAPH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0593); Low-frequency (popmax 1.07%, nfe).

How common is ODAPH p.Ser93Pro (c.277T>C) in the general population?

ODAPH p.Ser93Pro (c.277T>C) is low-frequency (popmax 1.07%, nfe) (gnomAD).

What do computational predictors say about ODAPH p.Ser93Pro (c.277T>C)?

AlphaMissense predicts likely benign (score 0.0593) — an in-silico prediction, not a clinical call.

ODAPH p.Ser93Pro

c.277T>C · rs140756390 · VCV788782

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0593 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0593	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.84	GERP 0.17
Regional constraint	o/e 0.97	unconstrained · MANE · 8,353 bp · p 0.74 · regional, not allelic
Overall
CADD	12.6	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 1.07% European (non-Finnish) · 12,593/1,180,028 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.895% 14,444/1,614,162 alleles · low-frequency exomes 13,421/1,461,882 · genomes 1,023/152,280 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.07%	94
Remaining individualsnot grpmax-eligible	0.795%	126
Finnishnot grpmax-eligible	0.632%	158
Ashkenazi Jewishnot grpmax-eligible	0.578%	173
Admixed American	0.548%	182
Middle Eastern	0.462%	216
South Asian	0.341%	293
African / African-American	0.143%	701
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00446%	22,441

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.Ser93Pro
Coding: c.277T>C
MANE Select: NM_178497
dbSNP: rs140756390
Type: single nucleotide variant
Location: chr4:75564323 (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

Similar variants

ODAPH c.67+138A>G Benign ★★ same type
ODAPH c.67+269A>C Benign ★★ same type
ODAPH p.Arg109His Benign ★★ same type
ODAPH p.Pro30Leu Benign ★★ same type
C4orf26 c.318G>A Likely pathogenic ★ same type
ODAPH p.Arg77Ter Pathogenic ★ same type
ODAPH p.Ile64= Uncertain significance ★ same type
ODAPH c.67+216A>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-ser93pro (accessed [today's date]).

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