Is ARMC5 p.Ser41Gly (c.121A>G) pathogenic?

ARMC5 p.Ser41Gly (c.121A>G) is classified Benign/Likely benign in ARMC5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0479); Rare (popmax 0.731%, eas).

How common is ARMC5 p.Ser41Gly (c.121A>G) in the general population?

ARMC5 p.Ser41Gly (c.121A>G) is rare (popmax 0.731%, eas) (gnomAD).

What do computational predictors say about ARMC5 p.Ser41Gly (c.121A>G)?

AlphaMissense predicts likely benign (score 0.0479) — an in-silico prediction, not a clinical call.

ARMC5 p.Ser41Gly

c.121A>G · rs539998802 · VCV731845

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0479 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.731%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0479	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.00	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 5.5	GERP -0.99, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 2,399 bp · p 1.1e-09 · regional, not allelic
Overall
CADD	16.5	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 0.731% East Asian · 327/44,734 alleles

Filtering AF 0.666% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.64%

Overall 0.0246% 392/1,592,310 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.731%	137
Remaining individualsnot grpmax-eligible	0.0921%	1,086
Admixed American	0.00174%	57,528
South Asian	0.0011%	90,690
European (non-Finnish)	0.00051%	196,140

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: ARMC5
Protein: p.Ser41Gly
Coding: c.121A>G
MANE Select: NM_001105247
dbSNP: rs539998802
Type: single nucleotide variant
Location: chr16:31459645 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 41: a UniProt-annotated variant site (in aimah2; uncertain significance); a UniProt-annotated variant site (in aimah2)

Full ARMC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC5 p.Arg173Ter Pathogenic ★★ same type
ARMC5 p.Ala55Val Uncertain significance ★★ ⚠ same type
ARMC5 p.Arg611Leu Uncertain significance ★★ ⚠ same type
ARMC5 p.Arg690Gln Uncertain significance ★★ ⚠ same type
ARMC5 p.Pro606Leu Uncertain significance ★★ ⚠ same type
ARMC5 p.Ser266Thr Uncertain significance ★★ ⚠ same type
ARMC5 p.Trp801Cys Uncertain significance ★★ ⚠ same type
ARMC5 p.Ala110Thr Benign/Likely benign ★★ 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/armc5-p-ser41gly (accessed [today's date]).

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