Is OFD1 p.Arg655Ser (c.1965A>T) pathogenic?

OFD1 p.Arg655Ser (c.1965A>T) is classified Uncertain significance in OFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: likely benign (0.3143); Absent from gnomAD v4.1.

How common is OFD1 p.Arg655Ser (c.1965A>T) in the general population?

OFD1 p.Arg655Ser (c.1965A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OFD1 p.Arg655Ser (c.1965A>T)?

AlphaMissense predicts likely benign (score 0.3143) — an in-silico prediction, not a clinical call.

OFD1 p.Arg655Ser

c.1965A>T · VCV4948952

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3143 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3143	likely benign
REVEL	0.606	indeterminate
SaProt	LLR 0.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 3.5, phastCons 0.79
Regional constraint	o/e 0.37	unconstrained · MANE · 125 bp · p 0.00034 · regional, not allelic
Overall
CADD	18.69	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Arg655Ser
Coding: c.1965A>T
MANE Select: NM_003611
Type: single nucleotide variant
Location: chrX:13760425 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 655: the 'mediates homooligomerization' region; the 'mediates the interaction with sdccag8' region

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

Similar variants

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
OFD1 p.Arg890Ter Pathogenic/Likely pathogenic ★★ same type
OFD1 p.Arg909Ter Pathogenic/Likely pathogenic ★★ same type
OFD1 p.Gln966Ter Pathogenic/Likely 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-arg655ser (accessed [today's date]).

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