Is ERRFI1 p.Pro348Thr (c.1042C>A) pathogenic?

ERRFI1 p.Pro348Thr (c.1042C>A) is classified Uncertain significance in ERRFI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: ambiguous (0.3763); Very rare (popmax 0.00935%, afr).

How common is ERRFI1 p.Pro348Thr (c.1042C>A) in the general population?

ERRFI1 p.Pro348Thr (c.1042C>A) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about ERRFI1 p.Pro348Thr (c.1042C>A)?

AlphaMissense predicts ambiguous (score 0.3763) — an in-silico prediction, not a clinical call.

ERRFI1 p.Pro348Thr

c.1042C>A · VCV3510273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3763	ambiguous
REVEL	0.224	benign-leaning
SaProt	LLR -8.20	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 8.6	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,406 bp · p 0.00016 · regional, not allelic
Overall
CADD	25.5	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 0.00935% African / African-American · 7/74,862 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000496% 8/1,613,926 alleles · very rare exomes 4/1,461,884 · genomes 4/152,042 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,695
European (non-Finnish)	8.47e-05%	1,180,027

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: ERRFI1
Protein: p.Pro348Thr
Coding: c.1042C>A
MANE Select: NM_018948
Type: single nucleotide variant
Location: chr1:8013557 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.20 · 7 PDB
Residue 348: the 'disordered' region; the 'interaction with egfr and erbb2 and regulation of egfr activation' region

Full ERRFI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERRFI1 p.Arg244= Benign ★★ same type
ERRFI1 p.Ile158Leu Benign ★★ same type
ERRFI1 p.Pro239Leu Benign ★★ same type
ERRFI1 p.Ala4Val Uncertain significance ★ ⚠ same type
ERRFI1 p.Ala8Thr Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg148Trp Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg245Lys Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg331Cys 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/errfi1-p-pro348thr (accessed [today's date]).

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