Is ERRFI1 p.Arg148Trp (c.442C>T) pathogenic?

ERRFI1 p.Arg148Trp (c.442C>T) is classified Uncertain significance in ERRFI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-09). AlphaMissense: likely benign (0.2516); Very rare (popmax 0.00439%, sas).

How common is ERRFI1 p.Arg148Trp (c.442C>T) in the general population?

ERRFI1 p.Arg148Trp (c.442C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about ERRFI1 p.Arg148Trp (c.442C>T)?

AlphaMissense predicts likely benign (score 0.2516) — an in-silico prediction, not a clinical call.

ERRFI1 p.Arg148Trp

c.442C>T · rs372669618 · VCV2347131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2516 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2516	likely benign
REVEL	0.398	indeterminate
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.57, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,406 bp · p 0.00016 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,084 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00335% 54/1,614,008 alleles · very rare exomes 49/1,461,888 · genomes 5/152,120 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,829
South Asiangrpmax	0.00439%	22,771
European (non-Finnish)	0.00381%	26,222
African / African-American	0.00267%	37,450

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg148Trp
Coding: c.442C>T
MANE Select: NM_018948
dbSNP: rs372669618
Type: single nucleotide variant
Location: chr1:8014157 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.20 · 7 PDB

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.Arg245Lys Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg331Cys Uncertain significance ★ same type
ERRFI1 p.Arg37Leu 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-arg148trp (accessed [today's date]).

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