Is RTF1 p.Gln671His (c.2013A>C) pathogenic?

RTF1 p.Gln671His (c.2013A>C) is classified Uncertain significance in RTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: ambiguous (0.3656); Ultra-rare (popmax 0.0111%, nfe).

How common is RTF1 p.Gln671His (c.2013A>C) in the general population?

RTF1 p.Gln671His (c.2013A>C) is ultra-rare (popmax 0.0111%, nfe) (gnomAD).

What do computational predictors say about RTF1 p.Gln671His (c.2013A>C)?

AlphaMissense predicts ambiguous (score 0.3656) — an in-silico prediction, not a clinical call.

RTF1 p.Gln671His

c.2013A>C · rs200907186 · VCV2285409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3656 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3656	ambiguous
REVEL	0.161	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -5.2, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 1,528 bp · p 5.6e-07 · regional, not allelic
Overall
CADD	19.62	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 0.0111% European (non-Finnish) · 130/1,176,036 alleles

Filtering AF 0.00947% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00891%

Overall 0.0082% 132/1,609,792 alleles · ultra-rare exomes 132/1,457,490 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0111%	9,046
Remaining individualsnot grpmax-eligible	0.00321%	31,159

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: RTF1
Protein: p.Gln671His
Coding: c.2013A>C
MANE Select: NM_015138
dbSNP: rs200907186
Type: single nucleotide variant
Location: chr15:41480312 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 18 PDB

Full RTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RTF1 p.Ala90Gly Uncertain significance ★ ⚠ same type
RTF1 p.Arg267Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg267Trp Uncertain significance ★ ⚠ same type
RTF1 p.Arg271Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg330Cys Uncertain significance ★ ⚠ same type
RTF1 p.Arg333Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg361Gln Uncertain significance ★ ⚠ same type
RTF1 p.Arg501Lys 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/rtf1-p-gln671his (accessed [today's date]).

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