Is ARMC7 p.Pro195Ser (c.583C>T) pathogenic?

ARMC7 p.Pro195Ser (c.583C>T) is classified Uncertain significance in ARMC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: likely benign (0.0681); Ultra-rare (popmax 0.016%, afr).

How common is ARMC7 p.Pro195Ser (c.583C>T) in the general population?

ARMC7 p.Pro195Ser (c.583C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about ARMC7 p.Pro195Ser (c.583C>T)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

ARMC7 p.Pro195Ser

c.583C>T · VCV3786278

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.3, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 19 kb · p 0.76 · regional, not allelic
Overall
CADD	18.04	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 0.016% African / African-American · 12/74,876 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000877% 14/1,597,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,240
Remaining individualsnot grpmax-eligible	0.00161%	62,280
European (non-Finnish)	8.48e-05%	1,178,746

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.Pro195Ser
Coding: c.583C>T
MANE Select: NM_024585
Type: single nucleotide variant
Location: chr17:75129024 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 3 PDB

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-pro195ser (accessed [today's date]).

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