Is ARMC2 p.Phe72Leu (c.214T>C) pathogenic?

ARMC2 p.Phe72Leu (c.214T>C) is classified Uncertain significance in ARMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). AlphaMissense: likely pathogenic (0.947); Very rare (popmax 0.00401%, afr).

How common is ARMC2 p.Phe72Leu (c.214T>C) in the general population?

ARMC2 p.Phe72Leu (c.214T>C) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about ARMC2 p.Phe72Leu (c.214T>C)?

AlphaMissense predicts likely pathogenic (score 0.947) — an in-silico prediction, not a clinical call.

ARMC2 p.Phe72Leu

c.214T>C · rs374802762 · VCV2551971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.947	likely pathogenic · top 1% in ARMC2
REVEL	0.408	indeterminate
SaProt	LLR -4.91	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 119 kb · p 0.00055 · regional, not allelic
Overall
CADD	25.2	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 0.00401% African / African-American · 3/74,884 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,612,762 alleles · very rare

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: ARMC2
Protein: p.Phe72Leu
Coding: c.214T>C
MANE Select: NM_032131
dbSNP: rs374802762
Type: single nucleotide variant
Location: chr6:108854481 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57
Residue 72: the 'disordered' region

Full ARMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC2 c.2153-1G>C Likely pathogenic ★ same type
ARMC2 p.Asn743Asp Likely pathogenic ★ same type
ARMC2 p.Ala123Val Uncertain significance ★ ⚠ same type
ARMC2 p.Ala143Thr Uncertain significance ★ ⚠ same type
ARMC2 p.Ala231Thr Uncertain significance ★ ⚠ same type
ARMC2 p.Ala260Pro Uncertain significance ★ ⚠ same type
ARMC2 p.Ala292Asp Uncertain significance ★ ⚠ same type
ARMC2 p.Ala495Val 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/armc2-p-phe72leu (accessed [today's date]).

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