Is FREM2 p.Asp2444= (c.7332C>T) pathogenic?

FREM2 p.Asp2444= (c.7332C>T) is classified Conflicting classifications of pathogenicity in FREM2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.012%, nfe); Associated with Fraser syndrome 2.

What condition is associated with FREM2 p.Asp2444= (c.7332C>T)?

FREM2 p.Asp2444= (c.7332C>T) is associated with Fraser syndrome 2 (ClinVar).

How common is FREM2 p.Asp2444= (c.7332C>T) in the general population?

FREM2 p.Asp2444= (c.7332C>T) is ultra-rare (popmax 0.012%, nfe) (gnomAD).

FREM2 p.Asp2444=

c.7332C>T · rs773197293 · VCV881618

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, nfe)

Conditions

Fraser syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -5.2
Overall
CADD	4.831	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% European (non-Finnish) · 142/1,180,040 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0098%

Overall 0.00973% 157/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.012%	8,310
Remaining individualsnot grpmax-eligible	0.0112%	8,927
African / African-American	0.004%	24,975
Admixed American	0.00333%	30,003
Finnishnot grpmax-eligible	0.00312%	32,017
South Asian	0.0011%	91,088

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: FREM2
Protein: p.Asp2444=
Coding: c.7332C>T
MANE Select: NM_207361
dbSNP: rs773197293
Type: single nucleotide variant
Location: chr13:38859403 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI <0.01 (gnomAD)
Residue 2444: a UniProt-annotated variant site (in cryptop)

Full FREM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fraser syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FREM2 p.Arg1355Ter Pathogenic/Likely pathogenic ★★ same condition
FREM2 p.Arg638Ter Likely pathogenic ★★ same condition
FREM2 p.Arg736Ter Pathogenic ★★ same condition
FREM2 p.Arg809Ter Pathogenic ★★ same condition
FREM2 p.Gln1051Ter Pathogenic/Likely pathogenic ★★ same condition
FREM2 p.Gln717Ter Likely pathogenic ★★ same condition
FREM2 p.Ala1659Thr Uncertain significance ★★ ⚠ same condition
FREM2 p.Ala1664Val Uncertain significance ★★ ⚠ same condition

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/frem2-p-asp2444 (accessed [today's date]).

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