Is OPHN1 p.Lys306Gln (c.916A>C) pathogenic?

OPHN1 p.Lys306Gln (c.916A>C) is classified Uncertain significance in OPHN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-01). AlphaMissense: likely pathogenic (0.5663); Absent from gnomAD v4.1.

How common is OPHN1 p.Lys306Gln (c.916A>C) in the general population?

OPHN1 p.Lys306Gln (c.916A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OPHN1 p.Lys306Gln (c.916A>C)?

AlphaMissense predicts likely pathogenic (score 0.5663) — an in-silico prediction, not a clinical call.

OPHN1 p.Lys306Gln

c.916A>C · rs2077560487 · VCV872372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5663 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5663	likely pathogenic
REVEL	0.214	benign-leaning
SaProt	LLR -10.02	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 137 kb · p 1.6e-11 · regional, not allelic
Overall
CADD	26.1	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: OPHN1
Protein: p.Lys306Gln
Coding: c.916A>C
MANE Select: NM_002547
dbSNP: rs2077560487
Type: single nucleotide variant
Location: chrX:68206590 (GRCh38)
Structure: AlphaFold pLDDT 74.86
Residue 306: the ph domain

Full OPHN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

OPHN1 c.1138+1G>A Pathogenic ★★ same type
OPHN1 c.1202-1G>A Likely pathogenic ★★ same type
OPHN1 c.155-2A>C Likely pathogenic ★★ same type
OPHN1 p.Arg243Trp Likely pathogenic ★★ ⚠ same type
OPHN1 p.Arg497Ter Pathogenic ★★ same type
OPHN1 p.Arg597Ter Pathogenic ★★ same type
OPHN1 p.Gln416Ter Pathogenic ★★ same type
OPHN1 p.Thr326Met 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/ophn1-p-lys306gln (accessed [today's date]).

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