Is OFD1 p.Ser435Arg (c.1303A>C) pathogenic?

OFD1 p.Ser435Arg (c.1303A>C) is classified Pathogenic in OFD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2001-03-01). AlphaMissense: likely benign (0.2991); Absent from gnomAD v4.1; Associated with orofaciodigital syndrome I.

What condition is associated with OFD1 p.Ser435Arg (c.1303A>C)?

OFD1 p.Ser435Arg (c.1303A>C) is associated with orofaciodigital syndrome I (ClinVar).

How common is OFD1 p.Ser435Arg (c.1303A>C) in the general population?

OFD1 p.Ser435Arg (c.1303A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OFD1 p.Ser435Arg (c.1303A>C)?

AlphaMissense predicts likely benign (score 0.2991) — an in-silico prediction, not a clinical call.

OFD1 p.Ser435Arg

c.1303A>C · rs122460150 · VCV11537

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

orofaciodigital syndrome I

Computational evidence

Protein change
AlphaMissense	0.2991	likely benign ⚠ discordant with ClinVar
REVEL	0.67	pathogenic-leaning
SaProt	LLR -7.90	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 2.1, phastCons 0.88
Regional constraint	o/e 0.93	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	17.42	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OFD1
Protein: p.Ser435Arg
Coding: c.1303A>C
MANE Select: NM_003611
dbSNP: rs122460150
Type: single nucleotide variant
Location: chrX:13756659 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 435: a UniProt-annotated variant site (in ofd1)

Full OFD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

orofaciodigital syndrome I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OFD1 c.1411+1G>A Pathogenic ★★ same condition
OFD1 c.2600-1G>C Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Arg367Ter Pathogenic ★★ same condition
OFD1 p.Arg41Ter Pathogenic ★★ same condition
OFD1 p.Arg890Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Arg909Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Tyr87Cys Pathogenic ★★ ⚠ same condition
OFD1 c.2388-3T>C 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/ofd1-p-ser435arg (accessed [today's date]).

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