Is SLC19A1 p.Val342Phe (c.1024G>T) pathogenic?

SLC19A1 p.Val342Phe (c.1024G>T) is classified Uncertain significance in SLC19A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely benign (0.2581); Rare (popmax 0.111%, amr).

How common is SLC19A1 p.Val342Phe (c.1024G>T) in the general population?

SLC19A1 p.Val342Phe (c.1024G>T) is rare (popmax 0.111%, amr) (gnomAD).

What do computational predictors say about SLC19A1 p.Val342Phe (c.1024G>T)?

AlphaMissense predicts likely benign (score 0.2581) — an in-silico prediction, not a clinical call.

SLC19A1 p.Val342Phe

c.1024G>T · rs142899279 · VCV1364488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2581 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2581	likely benign
REVEL	0.523	indeterminate
SaProt	LLR -9.51	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 0.73	GERP -3.4, phastCons 0.19
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.89 · regional, not allelic
Overall
CADD	17.99	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 0.111% Admixed American · 45/40,454 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.1%

Overall 0.0895% 1,325/1,480,186 alleles · rare exomes 1,206/1,328,574 · genomes 119/151,612 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.111%	899
European (non-Finnish)	0.107%	934
Remaining individualsnot grpmax-eligible	0.0957%	1,045
Middle Eastern	0.0361%	2,771
African / African-American	0.0192%	5,220
South Asian	0.0123%	8,112
Finnishnot grpmax-eligible	0.00868%	11,520

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: SLC19A1
Protein: p.Val342Phe
Coding: c.1024G>T
MANE Select: NM_194255
dbSNP: rs142899279
Type: single nucleotide variant
Location: chr21:45530897 (GRCh38)
Gene constraint: LOEUF 1.585 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.30 · 19 PDB
Residue 342: an α-helix

Full SLC19A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC19A1 p.Val342= Likely benign ★ same residue
COL18A1 p.Arg1081Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Arg915Ter Pathogenic/Likely pathogenic ★★ same type
RFC1 p.Arg383Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 c.*30G>A Uncertain significance ★★ same type
COL18A1 p.Ala1089Thr Uncertain significance ★★ ⚠ same type
COL18A1 p.Ala1254Val Uncertain significance ★★ ⚠ same type
COL18A1 p.Arg1081Gln 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/slc19a1-p-val342phe (accessed [today's date]).

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