Is SEMA4A p.His306Gln (c.918C>A) pathogenic?

SEMA4A p.His306Gln (c.918C>A) is classified Uncertain significance in SEMA4A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-20). AlphaMissense: ambiguous (0.4141); Absent from gnomAD v4.1.

How common is SEMA4A p.His306Gln (c.918C>A) in the general population?

SEMA4A p.His306Gln (c.918C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SEMA4A p.His306Gln (c.918C>A)?

AlphaMissense predicts ambiguous (score 0.4141) — an in-silico prediction, not a clinical call.

SEMA4A p.His306Gln

c.918C>A · rs761293482 · VCV2059178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4141 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4141	ambiguous
REVEL	0.234	benign-leaning
SaProt	LLR -6.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.91	GERP 0.38, phastCons 0.002
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.28 · regional, not allelic
Overall
CADD	22.3	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: SEMA4A
Protein: p.His306Gln
Coding: c.918C>A
MANE Select: NM_022367
dbSNP: rs761293482
Type: single nucleotide variant
Location: chr1:156161453 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.05
Residue 306: the sema domain

Full SEMA4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEMA4A p.His306Tyr Uncertain significance ★ ⚠ same residue
SEMA4A c.*208A>G Uncertain significance ★★ same type
SEMA4A p.Ala114Thr Uncertain significance ★★ ⚠ same type
SEMA4A p.Ala181Thr Uncertain significance ★★ ⚠ same type
SEMA4A p.Ala337Val Uncertain significance ★★ same type
SEMA4A p.Ala446Val Uncertain significance ★★ ⚠ same type
SEMA4A p.Ala509Gly Uncertain significance ★★ ⚠ same type
SEMA4A p.Ala570Thr Uncertain significance ★★ ⚠ 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/sema4a-p-his306gln (accessed [today's date]).

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