Is ARMC9 p.Ser85Phe (c.254C>T) pathogenic?

ARMC9 p.Ser85Phe (c.254C>T) is classified Uncertain significance in ARMC9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-30). AlphaMissense: likely benign (0.1121); Ultra-rare (popmax 0.0254%, afr).

How common is ARMC9 p.Ser85Phe (c.254C>T) in the general population?

ARMC9 p.Ser85Phe (c.254C>T) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about ARMC9 p.Ser85Phe (c.254C>T)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

ARMC9 p.Ser85Phe

c.254C>T · rs140272259 · VCV1366150

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -9.52	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 2.6	GERP -0.22, phastCons 0.023
Regional constraint	o/e 0.91	unconstrained · MANE · 165 kb · p 0.0061 · regional, not allelic
Overall
CADD	14.85	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 0.0254% African / African-American · 19/74,894 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00136% 22/1,613,984 alleles · ultra-rare exomes 9/1,461,876 · genomes 13/152,108 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,942
Admixed American	0.00333%	29,998
European (non-Finnish)	8.47e-05%	1,180,012

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: ARMC9
Protein: p.Ser85Phe
Coding: c.254C>T
MANE Select: NM_001352754
dbSNP: rs140272259
Type: single nucleotide variant
Location: chr2:231214907 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.71

Full ARMC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC9 c.1773+1G>A Likely pathogenic ★★ same type
ARMC9 c.178-1G>A Likely pathogenic ★★ same type
ARMC9 c.178-2A>C Likely pathogenic ★★ same type
ARMC9 p.Arg299Ter Pathogenic/Likely pathogenic ★★ same type
ARMC9 p.Arg343Cys Pathogenic/Likely pathogenic ★★ same type
ARMC9 p.Arg87Ter Pathogenic/Likely pathogenic ★★ same type
ARMC9 p.Thr293= Pathogenic/Likely pathogenic ★★ same type
ARMC9 p.Ala397Val 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/armc9-p-ser85phe (accessed [today's date]).

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