Is ERVFRD-1 p.Phe207Ser (c.620T>C) pathogenic?

ERVFRD-1 p.Phe207Ser (c.620T>C) is classified Uncertain significance in ERVFRD-1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: ambiguous (0.5216); Very rare (popmax 0.00266%, afr).

How common is ERVFRD-1 p.Phe207Ser (c.620T>C) in the general population?

ERVFRD-1 p.Phe207Ser (c.620T>C) is very rare (popmax 0.00266%, afr) (gnomAD).

What do computational predictors say about ERVFRD-1 p.Phe207Ser (c.620T>C)?

AlphaMissense predicts ambiguous (score 0.5216) — an in-silico prediction, not a clinical call.

ERVFRD-1 p.Phe207Ser

c.620T>C · VCV3276425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5216 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5216	ambiguous
REVEL	0.144	moderately benign-leaning
SaProt	LLR -5.07	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 0.65	phastCons 0.94
Regional constraint	o/e 0.86	unconstrained · MANE · 1,613 bp · p 0.00043 · regional, not allelic
Overall
CADD	11.35	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 0.00266% African / African-American · 2/75,050 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000137% 2/1,461,892 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: ERVFRD-1
Protein: p.Phe207Ser
Coding: c.620T>C
MANE Select: NM_207582
Type: single nucleotide variant
Location: chr6:11104691 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.71 · 3 PDB
Residue 207: a disulfide bond

Full ERVFRD-1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERVFRD-1 p.Ala15Val Uncertain significance ★ ⚠ same type
ERVFRD-1 p.Ala210Gly Uncertain significance ★ ⚠ same type
ERVFRD-1 p.Ala225Val Uncertain significance ★ ⚠ same type
ERVFRD-1 p.Ala70Val Uncertain significance ★ ⚠ same type
ERVFRD-1 p.Arg104Cys Uncertain significance ★ ⚠ same type
ERVFRD-1 p.Arg104His Uncertain significance ★ ⚠ same type
ERVFRD-1 p.Arg18His Uncertain significance ★ ⚠ same type
ERVFRD-1 p.Arg191Trp 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/ervfrd-1-p-phe207ser (accessed [today's date]).

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