Is ABITRAM p.Ile70Met (c.210C>G) pathogenic?

ABITRAM p.Ile70Met (c.210C>G) is classified Uncertain significance in ABITRAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely pathogenic (0.7118); Ultra-rare (popmax 0.0633%, amr).

How common is ABITRAM p.Ile70Met (c.210C>G) in the general population?

ABITRAM p.Ile70Met (c.210C>G) is ultra-rare (popmax 0.0633%, amr) (gnomAD).

What do computational predictors say about ABITRAM p.Ile70Met (c.210C>G)?

AlphaMissense predicts likely pathogenic (score 0.7118) — an in-silico prediction, not a clinical call.

ABITRAM p.Ile70Met

c.210C>G · rs200258029 · VCV2456513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7118 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0633%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7118	likely pathogenic
REVEL	0.587	indeterminate
SaProt	LLR -8.41	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 5,196 bp · p 0.73 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 0.0633% Admixed American · 38/60,002 alleles

Filtering AF 0.0474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0418%

Overall 0.00235% 38/1,613,972 alleles · ultra-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: ABITRAM
Protein: p.Ile70Met
Coding: c.210C>G
MANE Select: NM_017832
dbSNP: rs200258029
Type: single nucleotide variant
Location: chr9:108936386 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.21

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

Similar variants

ABITRAM p.Ala2Val Uncertain significance ★ ⚠ same type
ABITRAM p.Arg173His Uncertain significance ★ ⚠ same type
ABITRAM p.Arg22His Uncertain significance ★ ⚠ same type
ABITRAM p.Arg87Gln Uncertain significance ★ ⚠ same type
ABITRAM p.Arg87Trp Uncertain significance ★ ⚠ same type
ABITRAM p.Gln163Arg Uncertain significance ★ ⚠ same type
ABITRAM p.Gly106Asp Uncertain significance ★ ⚠ same type
ABITRAM p.Gly141Val 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/abitram-p-ile70met (accessed [today's date]).

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