Is ARMC3 p.Phe778Ser (c.2333T>C) pathogenic?

ARMC3 p.Phe778Ser (c.2333T>C) is classified Uncertain significance in ARMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.6523); Ultra-rare (popmax 0.0325%, nfe).

How common is ARMC3 p.Phe778Ser (c.2333T>C) in the general population?

ARMC3 p.Phe778Ser (c.2333T>C) is ultra-rare (popmax 0.0325%, nfe) (gnomAD).

What do computational predictors say about ARMC3 p.Phe778Ser (c.2333T>C)?

AlphaMissense predicts likely pathogenic (score 0.6523) — an in-silico prediction, not a clinical call.

ARMC3 p.Phe778Ser

c.2333T>C · rs369926323 · VCV2355566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6523 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0325%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6523	likely pathogenic
REVEL	0.151	moderately benign-leaning
SaProt	LLR -4.19	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.87, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 105 kb · p 0.0086 · regional, not allelic
Overall
CADD	22.0	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 0.0325% European (non-Finnish) · 383/1,179,478 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.0247% 399/1,613,172 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0325%	3,080
Middle Eastern	0.0165%	6,048
Remaining individualsnot grpmax-eligible	0.0112%	8,921
Admixed American	0.00667%	14,989
Finnishnot grpmax-eligible	0.00313%	31,987
African / African-American	0.00133%	74,990
South Asian	0.0011%	91,050

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.Phe778Ser
Coding: c.2333T>C
MANE Select: NM_173081
dbSNP: rs369926323
Type: single nucleotide variant
Location: chr10:23032947 (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-phe778ser (accessed [today's date]).

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