Is OFD1 p.Ser92Pro (c.274T>C) pathogenic?

OFD1 p.Ser92Pro (c.274T>C) is classified Likely pathogenic in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-09). AlphaMissense: likely pathogenic (0.8952); Absent from gnomAD v4.1.

How common is OFD1 p.Ser92Pro (c.274T>C) in the general population?

OFD1 p.Ser92Pro (c.274T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OFD1 p.Ser92Pro (c.274T>C)?

AlphaMissense predicts likely pathogenic (score 0.8952) — an in-silico prediction, not a clinical call.

OFD1 p.Ser92Pro

c.274T>C · VCV3338817

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8952 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8952	likely pathogenic ✓ concordant with ClinVar · top 1% in OFD1
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -12.69	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.30	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	27.3	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.Ser92Pro
Coding: c.274T>C
MANE Select: NM_003611
Type: single nucleotide variant
Location: chrX:13736640 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 92: the lish domain

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

Similar variants

OFD1 p.Ser92= Conflicting classifications of pathogenicity ★ same residue
OFD1 p.Ser92Phe Uncertain significance ★ ⚠ same residue
TRAPPC2 p.Glu92Asp Uncertain significance ★ ⚠ same residue
OFD1 c.1411+1G>A Pathogenic ★★ same type
OFD1 c.2600-1G>C Pathogenic/Likely pathogenic ★★ same type
OFD1 c.655-8A>G Likely pathogenic ★★ same type
OFD1 p.Arg367Ter Pathogenic ★★ same type
OFD1 p.Arg41Ter Pathogenic ★★ 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/ofd1-p-ser92pro (accessed [today's date]).

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