Is ARMC5 p.Pro33Ser (c.97C>T) pathogenic?

ARMC5 p.Pro33Ser (c.97C>T) is classified Conflicting classifications of pathogenicity in ARMC5 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0667); Rare (popmax 0.11%, amr); Associated with Inborn genetic diseases.

What condition is associated with ARMC5 p.Pro33Ser (c.97C>T)?

ARMC5 p.Pro33Ser (c.97C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARMC5 p.Pro33Ser (c.97C>T) in the general population?

ARMC5 p.Pro33Ser (c.97C>T) is rare (popmax 0.11%, amr) (gnomAD).

What do computational predictors say about ARMC5 p.Pro33Ser (c.97C>T)?

AlphaMissense predicts likely benign (score 0.0667) — an in-silico prediction, not a clinical call.

ARMC5 p.Pro33Ser

c.97C>T · rs200309618 · VCV2540432

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0667 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0667	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.37	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 0.67	GERP -3.8, phastCons 0.61
Regional constraint	o/e 1.40	unconstrained · MANE · 2,399 bp · p 1.1e-09 · regional, not allelic
Overall
CADD	14.95	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 0.11% Admixed American · 65/59,254 alleles

Filtering AF 0.0883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0817%

Overall 0.0758% 1,211/1,596,928 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.11%	912
European (non-Finnish)	0.0879%	1,138
Remaining individualsnot grpmax-eligible	0.0868%	1,152
Middle Eastern	0.0497%	2,013
South Asian	0.0386%	2,591
African / African-American	0.0174%	5,751
Ashkenazi Jewishnot grpmax-eligible	0.017%	5,884

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.Pro33Ser
Coding: c.97C>T
MANE Select: NM_001105247
dbSNP: rs200309618
Type: single nucleotide variant
Location: chr16:31459621 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 33: 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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARMC5 p.Ala55Val Uncertain significance ★★ ⚠ same condition
ARMC5 p.Arg611Leu Uncertain significance ★★ ⚠ same condition
ARMC5 p.Ser266Thr Uncertain significance ★★ ⚠ same condition
ARMC5 p.Trp801Cys Uncertain significance ★★ ⚠ same condition
ARMC5 p.Ala100Thr Uncertain significance ★ ⚠ same condition
ARMC5 p.Ala206Ser Uncertain significance ★ ⚠ same condition
ARMC5 p.Ala22Val Uncertain significance ★ ⚠ same condition
ARMC5 p.Ala243Gly Uncertain significance ★ ⚠ same condition

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-pro33ser (accessed [today's date]).

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