Is CNNM3 p.Phe71Val (c.211T>G) pathogenic?

CNNM3 p.Phe71Val (c.211T>G) is classified Uncertain significance in CNNM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: ambiguous (0.3457); Absent from gnomAD v4.1.

How common is CNNM3 p.Phe71Val (c.211T>G) in the general population?

CNNM3 p.Phe71Val (c.211T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNNM3 p.Phe71Val (c.211T>G)?

AlphaMissense predicts ambiguous (score 0.3457) — an in-silico prediction, not a clinical call.

CNNM3 p.Phe71Val

c.211T>G · VCV4230877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3457 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,458,142)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3457	ambiguous
REVEL	0.139	moderately benign-leaning
SaProt	LLR -5.25	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP -0.61, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 849 bp · p 0.0017 · regional, not allelic
Overall
CADD	22.3	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

No allele count reported in gnomAD v4.1 (AN 1,458,142). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CNNM3
Protein: p.Phe71Val
Coding: c.211T>G
MANE Select: NM_017623
Type: single nucleotide variant
Location: chr2:96816488 (GRCh38)
Gene constraint: LOEUF 1.23 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.63 · 7 PDB

Full CNNM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNNM3 p.Ala221Gly Uncertain significance ★★ ⚠ same type
CNNM3 p.Ala128Val Uncertain significance ★ ⚠ same type
CNNM3 p.Ala142Thr Uncertain significance ★ ⚠ same type
CNNM3 p.Ala146Val Uncertain significance ★ ⚠ same type
CNNM3 p.Ala158Thr Uncertain significance ★ ⚠ same type
CNNM3 p.Ala162Glu Uncertain significance ★ ⚠ same type
CNNM3 p.Ala176Thr Uncertain significance ★ ⚠ same type
CNNM3 p.Ala191Thr 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/cnnm3-p-phe71val (accessed [today's date]).

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