Is ARMCX2 p.Val98= (c.294G>T) pathogenic?

ARMCX2 p.Val98= (c.294G>T) is classified Likely benign in ARMCX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). Ultra-rare (popmax 0.0474%, nfe).

How common is ARMCX2 p.Val98= (c.294G>T) in the general population?

ARMCX2 p.Val98= (c.294G>T) is ultra-rare (popmax 0.0474%, nfe) (gnomAD).

ARMCX2 p.Val98=

c.294G>T · rs372074769 · VCV2661070

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0474%, 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 -0.75
Overall
CADD	4.267	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0474% European (non-Finnish) · 423/893,051 alleles

Filtering AF 0.0436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0421%

Overall 0.0361% 436/1,208,216 alleles · ultra-rare exomes 407/1,095,223 · genomes 29/112,993 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0474%	2,111
Remaining individualsnot grpmax-eligible	0.0211%	4,746
African / African-American	0.00522%	19,149

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: ARMCX2
Protein: p.Val98=
Coding: c.294G>T
MANE Select: NM_177949
dbSNP: rs372074769
Type: single nucleotide variant
Location: chrX:101657295 (GRCh38)
Structure: AlphaFold pLDDT 64.69
Residue 98: the 'disordered' region

Full ARMCX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMCX2 p.Ala105Pro Uncertain significance ★ ⚠ same type
ARMCX2 p.Ala105Thr Uncertain significance ★ ⚠ same type
ARMCX2 p.Ala115Ser Uncertain significance ★ ⚠ same type
ARMCX2 p.Ala133Thr Uncertain significance ★ ⚠ same type
ARMCX2 p.Ala170Gly Uncertain significance ★ ⚠ same type
ARMCX2 p.Ala175Thr Uncertain significance ★ ⚠ same type
ARMCX2 p.Ala18Ser Uncertain significance ★ ⚠ same type
ARMCX2 p.Arg288Gly 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/armcx2-p-val98 (accessed [today's date]).

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