Is OFD1 p.Ala148Pro (c.442G>C) pathogenic?

OFD1 p.Ala148Pro (c.442G>C) is classified Likely pathogenic in OFD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-10). AlphaMissense: likely pathogenic (0.6809); Absent from gnomAD v4.1; Associated with OFD1-related disorder.

What condition is associated with OFD1 p.Ala148Pro (c.442G>C)?

OFD1 p.Ala148Pro (c.442G>C) is associated with OFD1-related disorder (ClinVar).

How common is OFD1 p.Ala148Pro (c.442G>C) in the general population?

OFD1 p.Ala148Pro (c.442G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OFD1 p.Ala148Pro (c.442G>C)?

AlphaMissense predicts likely pathogenic (score 0.6809) — an in-silico prediction, not a clinical call.

OFD1 p.Ala148Pro

c.442G>C · rs2518821166 · VCV3031535

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6809 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

OFD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.6809	likely pathogenic ✓ concordant with ClinVar · top 4% in OFD1
REVEL	0.538	indeterminate
SaProt	LLR -11.90	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	22.1	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.Ala148Pro
Coding: c.442G>C
MANE Select: NM_003611
dbSNP: rs2518821166
Type: single nucleotide variant
Location: chrX:13744444 (GRCh38)
Structure: AlphaFold pLDDT 68.41

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

Disease context

OFD1-related disorder

Similar variants

OFD1 c.655-8A>G Likely pathogenic ★★ same condition
OFD1 p.Arg909Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Gln966Ter Pathogenic/Likely pathogenic ★★ same condition
TRAPPC2 p.Ser73Leu Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Asn610Lys Uncertain significance ★★ ⚠ same condition
OFD1 p.Asp371Asn Uncertain significance ★★ ⚠ same condition
OFD1 p.Leu707Phe Uncertain significance ★★ ⚠ same condition
OFD1 c.382-2A>G Likely pathogenic ★ 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-ala148pro (accessed [today's date]).

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