Is ARMC3 p.Glu122Val (c.365A>T) pathogenic?

ARMC3 p.Glu122Val (c.365A>T) is classified Uncertain significance in ARMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely benign (0.3078); Ultra-rare (popmax 0.0228%, sas).

How common is ARMC3 p.Glu122Val (c.365A>T) in the general population?

ARMC3 p.Glu122Val (c.365A>T) is ultra-rare (popmax 0.0228%, sas) (gnomAD).

What do computational predictors say about ARMC3 p.Glu122Val (c.365A>T)?

AlphaMissense predicts likely benign (score 0.3078) — an in-silico prediction, not a clinical call.

ARMC3 p.Glu122Val

c.365A>T · VCV3947638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3078 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0228%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3078	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.44	acceptor loss, 3 bp away · masked 0 · deltas
Pangolin	Δ0.33	loss · gain 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.9	GERP 0.54, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 105 kb · p 0.0086 · regional, not allelic
Overall
CADD	25.9	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 0.0228% South Asian · 20/87,834 alleles

Filtering AF 0.015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.00362% 58/1,600,738 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0622%	1,607
South Asiangrpmax	0.0228%	4,392
Remaining individualsnot grpmax-eligible	0.0129%	7,743
African / African-American	0.00405%	24,708
Admixed American	0.00177%	56,460
European (non-Finnish)	0.00068%	146,988

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ARMC3
Protein: p.Glu122Val
Coding: c.365A>T
MANE Select: NM_173081
Type: single nucleotide variant
Location: chr10:22959402 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.81

Full ARMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC3 p.Met441Ile Uncertain significance ★★ ⚠ same type
ARMC3 c.916+1G>A Uncertain significance ★ same type
ARMC3 p.Ala115Asp Uncertain significance ★ ⚠ same type
ARMC3 p.Ala118Thr Uncertain significance ★ ⚠ same type
ARMC3 p.Ala138Ser Uncertain significance ★ ⚠ same type
ARMC3 p.Ala192Ser Uncertain significance ★ ⚠ same type
ARMC3 p.Ala211Val Uncertain significance ★ ⚠ same type
ARMC3 p.Ala335Thr 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/armc3-p-glu122val (accessed [today's date]).

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