Is ARMC3 p.Ser327Phe (c.980C>T) pathogenic?

ARMC3 p.Ser327Phe (c.980C>T) is classified Uncertain significance in ARMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.2101); Ultra-rare (popmax 0.0574%, afr).

How common is ARMC3 p.Ser327Phe (c.980C>T) in the general population?

ARMC3 p.Ser327Phe (c.980C>T) is ultra-rare (popmax 0.0574%, afr) (gnomAD).

What do computational predictors say about ARMC3 p.Ser327Phe (c.980C>T)?

AlphaMissense predicts likely benign (score 0.2101) — an in-silico prediction, not a clinical call.

ARMC3 p.Ser327Phe

c.980C>T · rs375449942 · VCV2468595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2101 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0574%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2101	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -10.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 105 kb · p 0.0086 · regional, not allelic
Overall
CADD	24.5	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 0.0574% African / African-American · 43/74,978 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.039%

Overall 0.00304% 49/1,613,866 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0574%	1,744
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Admixed American	0.00333%	29,993

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: ARMC3
Protein: p.Ser327Phe
Coding: c.980C>T
MANE Select: NM_173081
dbSNP: rs375449942
Type: single nucleotide variant
Location: chr10:22981403 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.81

Full ARMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC3 p.Met441Ile Uncertain significance ★★ ⚠ same type
ARMC3 c.916+1G>A Uncertain significance ★ same type
ARMC3 p.Ala115Asp Uncertain significance ★ ⚠ same type
ARMC3 p.Ala118Thr Uncertain significance ★ ⚠ same type
ARMC3 p.Ala138Ser Uncertain significance ★ ⚠ same type
ARMC3 p.Ala192Ser Uncertain significance ★ ⚠ same type
ARMC3 p.Ala211Val Uncertain significance ★ ⚠ same type
ARMC3 p.Ala335Thr 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/armc3-p-ser327phe (accessed [today's date]).

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