Is ARMC5 p.Pro347Ser (c.1039C>T) pathogenic?

ARMC5 p.Pro347Ser (c.1039C>T) is classified Benign in ARMC5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-05-04). AlphaMissense: likely benign (0.1632); Rare (popmax 0.508%, eas).

How common is ARMC5 p.Pro347Ser (c.1039C>T) in the general population?

ARMC5 p.Pro347Ser (c.1039C>T) is rare (popmax 0.508%, eas) (gnomAD).

What do computational predictors say about ARMC5 p.Pro347Ser (c.1039C>T)?

AlphaMissense predicts likely benign (score 0.1632) — an in-silico prediction, not a clinical call.

ARMC5 p.Pro347Ser

c.1039C>T · rs79238971 · VCV1686514

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1632 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.508%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1632	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -6.12	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 6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,961 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	21.2	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 0.508% East Asian · 228/44,890 alleles

Filtering AF 0.454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.433%

Overall 0.0143% 231/1,612,764 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.508%	197
Remaining individualsnot grpmax-eligible	0.0048%	20,830

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.Pro347Ser
Coding: c.1039C>T
MANE Select: NM_001105247
dbSNP: rs79238971
Type: single nucleotide variant
Location: chr16:31462586 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 347: 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-pro347ser (accessed [today's date]).

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