Is SP7 p.His348= (c.1044C>T) pathogenic?

SP7 p.His348= (c.1044C>T) is classified Likely benign in SP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-23). Very rare (popmax 0.000678%, nfe).

How common is SP7 p.His348= (c.1044C>T) in the general population?

SP7 p.His348= (c.1044C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

SP7 p.His348=

c.1044C>T · VCV3712626

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1, phastCons 1
Overall
CADD	7.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,828 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,798 alleles · very rare

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: SP7
Protein: p.His348=
Coding: c.1044C>T
MANE Select: NM_001173467
Type: single nucleotide variant
Location: chr12:53328398 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 52.78

Full SP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SP7 p.Ala2Val Uncertain significance ★★ ⚠ same type
SP7 p.Arg267Cys Uncertain significance ★★ ⚠ same type
SP7 p.Arg280Leu Uncertain significance ★★ ⚠ same type
SP7 p.Arg280Trp Uncertain significance ★★ ⚠ same type
SP7 p.Arg316His Uncertain significance ★★ ⚠ same type
SP7 p.Arg350Trp Uncertain significance ★★ ⚠ same type
SP7 p.Arg362His Uncertain significance ★★ ⚠ same type
SP7 p.Arg365Ter 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/sp7-p-his348 (accessed [today's date]).

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