Is BORCS5 p.Ile118Met (c.354C>G) pathogenic?

BORCS5 p.Ile118Met (c.354C>G) is classified Uncertain significance in BORCS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: ambiguous (0.3588); Very rare (popmax 0.00223%, eas).

How common is BORCS5 p.Ile118Met (c.354C>G) in the general population?

BORCS5 p.Ile118Met (c.354C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BORCS5 p.Ile118Met (c.354C>G)?

AlphaMissense predicts ambiguous (score 0.3588) — an in-silico prediction, not a clinical call.

BORCS5 p.Ile118Met

c.354C>G · rs1329843882 · VCV3134773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3588 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3588	ambiguous
REVEL	0.217	benign-leaning
SaProt	LLR -9.42	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 108 kb · p 0.7 · regional, not allelic
Overall
CADD	23.4	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 0.00223% East Asian · 1/44,764 alleles

Overall 6.85e-05% 1/1,459,064 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: BORCS5
Protein: p.Ile118Met
Coding: c.354C>G
MANE Select: NM_058169
dbSNP: rs1329843882
Type: single nucleotide variant
Location: chr12:12435779 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.54

Full BORCS5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BORCS5 p.Ala154Thr Uncertain significance ★ ⚠ same type
BORCS5 p.Ala79Asp Uncertain significance ★ ⚠ same type
BORCS5 p.Arg157His Uncertain significance ★ ⚠ same type
BORCS5 p.Arg158His Uncertain significance ★ ⚠ same type
BORCS5 p.Arg182Gln Uncertain significance ★ ⚠ same type
BORCS5 p.Arg182Trp Uncertain significance ★ ⚠ same type
BORCS5 p.Arg192Cys Uncertain significance ★ ⚠ same type
BORCS5 p.Arg192His 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/borcs5-p-ile118met (accessed [today's date]).

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