Is CSMD3 p.Phe1702Val (c.5104T>G) pathogenic?

CSMD3 p.Phe1702Val (c.5104T>G) is classified Uncertain significance in CSMD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-20). AlphaMissense: likely pathogenic (0.8396); Ultra-rare (popmax 0.0156%, eas).

How common is CSMD3 p.Phe1702Val (c.5104T>G) in the general population?

CSMD3 p.Phe1702Val (c.5104T>G) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about CSMD3 p.Phe1702Val (c.5104T>G)?

AlphaMissense predicts likely pathogenic (score 0.8396) — an in-silico prediction, not a clinical call.

CSMD3 p.Phe1702Val

c.5104T>G · rs760128306 · VCV3078235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8396 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Computational evidence

Protein change
AlphaMissense	0.8396	likely pathogenic
REVEL	0.439	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 442 kb · p 0.031 · regional, not allelic
Overall
CADD	26.1	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 0.0156% East Asian · 7/44,872 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000496% 8/1,613,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,410
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: CSMD3
Protein: p.Phe1702Val
Coding: c.5104T>G
MANE Select: NM_198123
dbSNP: rs760128306
Type: single nucleotide variant
Location: chr8:112492663 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.97 (gnomAD)
Residue 1702: a disulfide bond; the sushi 9 domain

Full CSMD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSMD3 p.Glu2761Val Uncertain significance ★★ same type
CSMD3 p.Leu3027Phe Uncertain significance ★★ same type
CSMD3 c.4896-3C>T Benign ★★ same type
CSMD3 p.Arg1020His Benign ★★ same type
CSMD3 p.Arg1228Gln Likely benign ★★ same type
CSMD3 p.Arg687= Benign/Likely benign ★★ same type
CSMD3 p.Asp1025= Benign ★★ same type
CSMD3 p.Asp1473= 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/csmd3-p-phe1702val (accessed [today's date]).

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