Is FREM2 p.Pro82Ser (c.244C>T) pathogenic?

FREM2 p.Pro82Ser (c.244C>T) is classified Uncertain significance in FREM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely benign (0.3009); No allele count reported in gnomAD v4.1 (AN 1,607,736); Associated with Fraser syndrome 2.

What condition is associated with FREM2 p.Pro82Ser (c.244C>T)?

FREM2 p.Pro82Ser (c.244C>T) is associated with Fraser syndrome 2, isolated cryptophthalmia (ClinVar).

How common is FREM2 p.Pro82Ser (c.244C>T) in the general population?

FREM2 p.Pro82Ser (c.244C>T) is no allele count reported in gnomAD v4.1 (AN 1,607,736) (gnomAD).

What do computational predictors say about FREM2 p.Pro82Ser (c.244C>T)?

AlphaMissense predicts likely benign (score 0.3009) — an in-silico prediction, not a clinical call.

FREM2 p.Pro82Ser

c.244C>T · VCV3575949

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3009 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,736)

Conditions

Fraser syndrome 2

Computational evidence

Protein change
AlphaMissense	0.3009	likely benign
REVEL	0.385	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 169 kb · p 0.0054 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,607,736). 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: FREM2
Protein: p.Pro82Ser
Coding: c.244C>T
MANE Select: NM_207361
Type: single nucleotide variant
Location: chr13:38687588 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI <0.01 (gnomAD)

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

Also linked: isolated cryptophthalmia

Similar variants

FREM2 p.Pro82Leu Uncertain significance ★ same residue
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

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-pro82ser (accessed [today's date]).

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