Is OFD1 p.Phe828Val (c.2482T>G) pathogenic?

OFD1 p.Phe828Val (c.2482T>G) is classified Benign/Likely benign in OFD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-03). AlphaMissense: likely benign (0.0978); Ultra-rare (popmax 0.0416%, amr); Associated with orofaciodigital syndrome I.

What condition is associated with OFD1 p.Phe828Val (c.2482T>G)?

OFD1 p.Phe828Val (c.2482T>G) is associated with orofaciodigital syndrome I, Simpson-Golabi-Behmel syndrome type 2, retinitis pigmentosa 23 (ClinVar).

How common is OFD1 p.Phe828Val (c.2482T>G) in the general population?

OFD1 p.Phe828Val (c.2482T>G) is ultra-rare (popmax 0.0416%, amr) (gnomAD).

What do computational predictors say about OFD1 p.Phe828Val (c.2482T>G)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

OFD1 p.Phe828Val

c.2482T>G · rs779051357 · VCV568118

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0416%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

orofaciodigital syndrome I

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -6.25	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 1.1	GERP 5.1, phastCons 0.98
Regional constraint	o/e 1.02	unconstrained · MANE · 8,639 bp · p 0.77 · regional, not allelic
Overall
CADD	18.87	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 0.0416% Admixed American · 19/45,711 alleles

Filtering AF 0.0272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0226%

Overall 0.00168% 19/1,133,274 alleles · ultra-rare exomes 16/1,020,618 · genomes 3/112,656 · joint denominator

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: OFD1
Protein: p.Phe828Val
Coding: c.2482T>G
MANE Select: NM_003611
dbSNP: rs779051357
Type: single nucleotide variant
Location: chrX:13762438 (GRCh38)
Structure: AlphaFold pLDDT 68.41
Residue 828: the 'mediates the interaction with sdccag8' region; the 'disordered' region

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

Also linked: Simpson-Golabi-Behmel syndrome type 2 retinitis pigmentosa 23 Joubert syndrome 10 Joubert syndrome

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.Gln966Ter Pathogenic/Likely pathogenic ★★ same condition
OFD1 p.Tyr87Cys 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-phe828val (accessed [today's date]).

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