Is ARMC7 p.Ser108Ala (c.322T>G) pathogenic?

ARMC7 p.Ser108Ala (c.322T>G) is classified Uncertain significance in ARMC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.1344); Ultra-rare (popmax 0.0156%, eas).

How common is ARMC7 p.Ser108Ala (c.322T>G) in the general population?

ARMC7 p.Ser108Ala (c.322T>G) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about ARMC7 p.Ser108Ala (c.322T>G)?

AlphaMissense predicts likely benign (score 0.1344) — an in-silico prediction, not a clinical call.

ARMC7 p.Ser108Ala

c.322T>G · VCV3315718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1344 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1344	likely benign
REVEL	0.518	indeterminate
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.41, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 19 kb · p 0.76 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,860 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000479% 7/1,461,262 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: ARMC7
Protein: p.Ser108Ala
Coding: c.322T>G
MANE Select: NM_024585
Type: single nucleotide variant
Location: chr17:75128763 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 3 PDB
Residue 108: an α-helix

Full ARMC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC7 p.Ala181Val Uncertain significance ★ ⚠ same type
ARMC7 p.Ala19Glu Uncertain significance ★ ⚠ same type
ARMC7 p.Arg130Cys Uncertain significance ★ ⚠ same type
ARMC7 p.Arg147Cys Uncertain significance ★ ⚠ same type
ARMC7 p.Arg147His Uncertain significance ★ ⚠ same type
ARMC7 p.Arg155Ser Uncertain significance ★ ⚠ same type
ARMC7 p.Arg155Thr Uncertain significance ★ ⚠ same type
ARMC7 p.Arg157Trp 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/armc7-p-ser108ala (accessed [today's date]).

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